Endothelium as a Therapeutic Target in Diabetes Mellitus: From Basic Mechanisms to Clinical Practice

doi:10.2174/0929867326666190119154152
摘要

内皮通过调节动脉血压，分配营养素和激素以及提供调节凝血，纤维蛋白溶解和炎症的光滑表面，在人类体内平衡中起着至关重要的作用。血管内皮功能障碍存在于糖尿病（DM）中，并有助于大血管疾病的发展和进展，同时也与大多数微血管并发症（如糖尿病性视网膜病，肾病和神经病）有关。高血糖，胰岛素抵抗，高胰岛素血症和血脂异常是内皮功能障碍发病机理中的主要因素。关于抗糖尿病药物，二甲双胍，格列齐特，吡格列酮，艾塞那肽和达格列净对血管内皮功能（EF）产生有益作用；格列美脲和格列本脲，二肽基肽酶-4抑制剂和利拉鲁肽具有中性作用，而研究胰岛素类似物，依帕列净和卡那列净对EF影响的研究有限。在降脂药物方面，他汀类药物可改善DM患者的EF，而短期试验的数据表明非诺贝特可改善EF。依折麦布也可以改善EF，但需要对DM患者进行进一步的研究。乙酰水杨酸对EF的作用是剂量依赖性的，较低的剂量可以改善EF，而较高的剂量则不能。氯吡格雷可改善EF，但需要在DM受试者中进行更多研究。此外，血管紧张素转化酶抑制剂/血管紧张素II受体阻滞剂可改善EF。 5型磷酸二酯酶抑制剂可改善海绵体中的EF。最后，西洛他唑对EF有良好的作用，但是，DM患者还需要更多数据。
关键词: 内皮，糖尿病，糖尿病并发症，抗糖尿病药，降脂药，抗血小板药，降压药。
« Previous Next »
[1] 
Rajendran, P.; Rengarajan, T.; Thangavel, J.; Nishigaki, Y.; Sakthisekaran, D.; Sethi, G.; Nishigaki, I. The vascular endothelium and human diseases. Int. J. Biol. Sci.,  2013, 9(10), 1057-1069.
[http://dx.doi.org/10.7150/ijbs.7502] [PMID: 24250251 ] 
[2] 
Potenza, M.A.; Gagliardi, S.; Nacci, C.; Carratu’, M.R.; Montagnani, M. Endothelial dysfunction in diabetes: from mechanisms to therapeutic targets. Curr. Med. Chem.,  2009, 16(1), 94-112.
[http://dx.doi.org/10.2174/092986709787002853] [PMID: 19149564 ] 
[3] 
Roberts, A.C.; Porter, K.E. Cellular and molecular mechanisms of endothelial dysfunction in diabetes. Diab. Vasc. Dis. Res.,  2013, 10(6), 472-482.
[http://dx.doi.org/10.1177/1479164113500680] [PMID: 24002671 ] 
[4] 
Michiels, C. Endothelial cell functions. J. Cell. Physiol.,  2003, 196(3), 430-443.
[http://dx.doi.org/10.1002/jcp.10333] [PMID: 12891700 ] 
[5] 
Jia, G.; Durante, W.; Sowers, J.R. Endothelium-derived hyperpolarizing factors: a potential therapeutic target for vascular dysfunction in obesity and insulin resistance. Diabetes,  2016, 65(8), 2118-2120.
[http://dx.doi.org/10.2337/dbi16-0026] [PMID: 27456617 ] 
[6] 
Tousoulis, D.; Kampoli, A.M.; Tentolouris, C.; Papageorgiou, N.; Stefanadis, C. The role of nitric oxide on endothelial function. Curr. Vasc. Pharmacol.,  2012, 10(1), 4-18.
[http://dx.doi.org/10.2174/157016112798829760] [PMID: 22112350 ] 
[7] 
Palmer, R.M.; Ashton, D.S.; Moncada, S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature,  1988, 333(6174), 664-666.
[http://dx.doi.org/10.1038/333664a0] [PMID: 3131684 ] 
[8] 
Joannides, R.; Haefeli, W.E.; Linder, L.; Richard, V.; Bak-kali, E.H.; Thuillez, C.; Lüscher, T.F. Nitric oxide is respon-sible for flow-dependent dilatation of human peripheral con-duit arteries in vivo. Circulation,  1995, 91(5), 1314-1319.
[http://dx.doi.org/10.1161/01.CIR.91.5.1314] [PMID: 7867167 ] 
[9] 
Münzel, T.; Feil, R.; Mülsch, A.; Lohmann, S.M.; Hofmann, F.; Walter, U. Physiology and pathophysiology of vascular signaling controlled by guanosine 3′,5′-cyclic monophosphate-dependent protein kinase. Circulation,  2003, 108(18), 2172-2183.
[http://dx.doi.org/10.1161/01.CIR.0000094403.78467.C3] [PMID: 14597579 ] 
[10] 
Mitchell, J.A.; Ali, F.; Bailey, L.; Moreno, L.; Harrington, L.S. Role of nitric oxide and prostacyclin as vasoactive hormones released by the endothelium. Exp. Physiol.,  2008, 93(1), 141-147.
[http://dx.doi.org/10.1113/expphysiol.2007.038588] [PMID: 17965142 ] 
[11] 
Haynes, W.G.; Webb, D.J. Contribution of endogenous generation of endothelin-1 to basal vascular tone. Lancet,  1994, 344(8926), 852-854.
[http://dx.doi.org/10.1016/S0140-6736(94)92827-4] [PMID: 7916401 ] 
[12] 
Masaki, T.; Sawamura, T. Endothelin and endothelial dysfunction. Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci.,  2006, 82(1), 17-24.
[http://dx.doi.org/10.2183/pjab.82.17] [PMID: 25792766 ] 
[13] 
Sampaio Storch, A.; Mattos, J.D.; Galdino, S.; Miguens Rocha, H.N. Methods of endothelial function assessment: description and applications. Int. J. Cardiovasc. Sci.,  2017, 30(3), 262-273.
[14] 
Lekakis, J.; Abraham, P.; Balbarini, A.; Blann, A.; Boulanger, C.M.; Cockcroft, J.; Cosentino, F.; Deanfield, J.; Gallino, A.; Ikonomidis, I.; Kremastinos, D.; Landmesser, U.; Protogerou, A.; Stefanadis, C.; Tousoulis, D.; Vassalli, G.; Vink, H.; Werner, N.; Wilkinson, I.; Vlachopoulos, C. Methods for evaluating endothelial function: a position statement from the European society of cardiology working group on peripheral circulation. Eur. J. Cardiovasc. Prev. Rehabil.,  2011, 18(6), 775-789.
[http://dx.doi.org/10.1177/1741826711398179] [PMID: 21450600 ] 
[15] 
Flammer, A.J.; Anderson, T.; Celermajer, D.S.; Creager, M.A.; Deanfield, J.; Ganz, P.; Hamburg, N.M.; Lüscher, T.F.; Shechter, M.; Taddei, S.; Vita, J.A.; Lerman, A. The assessment of endothelial function: from research into clinical practice. Circulation,  2012, 126(6), 753-767.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.112.093245] [PMID: 22869857 ] 
[16] 
Tousoulis, D.; Papageorgiou, N.; Androulakis, E.; Siasos, G.; Latsios, G.; Tentolouris, K.; Stefanadis, C. Diabetes mellitus-associated vascular impairment: novel circulating biomarkers and therapeutic approaches. J. Am. Coll. Cardiol.,  2013, 62(8), 667-676.
[http://dx.doi.org/10.1016/j.jacc.2013.03.089] [PMID: 23948511 ] 
[17] 
Tousoulis, D.; Androulakis, E.; Papageorgiou, N.; Siasos, G.; Latsios, G.; Charakida, M.; Kampoli, A.M.; Oikonomou, E.; Stefanadis, C. Novel biomarkers assessing endothelial dysfunction: role of microRNAs. Curr. Top. Med. Chem.,  2013, 13(13), 1518-1526.
[http://dx.doi.org/10.2174/15680266113139990100] [PMID: 23745803 ] 
[18] 
Tabit, C.E.; Chung, W.B.; Hamburg, N.M.; Vita, J.A. Endothelial dysfunction in diabetes mellitus: molecular mechanisms and clinical implications. Rev. Endocr. Metab. Disord.,  2010, 11(1), 61-74.
[http://dx.doi.org/10.1007/s11154-010-9134-4] [PMID: 20186491 ] 
[19] 
UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet,  1998, 352(9131), 854-865.
[http://dx.doi.org/10.1016/S0140-6736(98)07037-8] [PMID: 9742977 ] 
[20] 
Bakker, W.; Eringa, E.C.; Sipkema, P.; van Hinsbergh, V.W. Endothelial dysfunction and diabetes: roles of hyperglycemia, impaired insulin signaling and obesity. Cell Tissue Res.,  2009, 335(1), 165-189.
[http://dx.doi.org/10.1007/s00441-008-0685-6] [PMID: 18941783 ] 
[21] 
Brownlee, M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes,  2005, 54(6), 1615-1625.
[http://dx.doi.org/10.2337/diabetes.54.6.1615] [PMID: 15919781 ] 
[22] 
Greene, D.A.; Lattimer, S.A.; Sima, A.A. Sorbitol, phosphoinositides, and sodium-potassium-ATPase in the pathogenesis of diabetic complications. N. Engl. J. Med.,  1987, 316(10), 599-606.
[http://dx.doi.org/10.1056/NEJM198703053161007] [PMID: 3027558 ] 
[23] 
Barnett, P.A.; González, R.G.; Chylack, L.T. Jr.; Cheng, H.M. The effect of oxidation on sorbitol pathway kinetics. Diabetes,  1986, 35(4), 426-432.
[http://dx.doi.org/10.2337/diab.35.4.426] [PMID: 3956880 ] 
[24] 
Oyama, T.; Miyasita, Y.; Watanabe, H.; Shirai, K. The role of polyol pathway in high glucose-induced endothelial cell damages. Diabetes Res. Clin. Pract.,  2006, 73(3), 227-234.
[http://dx.doi.org/10.1016/j.diabres.2006.02.010] [PMID: 16624439 ] 
[25] 
Chilelli, N.C.; Burlina, S.; Lapolla, A. AGEs, rather than hyperglycemia, are responsible for microvascular complications in diabetes: a “glycoxidation-centric” point of view. Nutr. Metab. Cardiovasc. Dis.,  2013, 23(10), 913-919.
[http://dx.doi.org/10.1016/j.numecd.2013.04.004] [PMID: 23786818 ] 
[26] 
Stirban, A.; Gawlowski, T.; Roden, M. Vascular effects of advanced glycation endproducts: Clinical effects and molecular mechanisms. Mol. Metab.,  2013, 3(2), 94-108.
[http://dx.doi.org/10.1016/j.molmet.2013.11.006] [PMID: 24634815 ] 
[27] 
Schmidt, A.M.; Hori, O.; Chen, J.X.; Li, J.F.; Crandall, J.; Zhang, J.; Cao, R.; Yan, S.D.; Brett, J.; Stern, D. Advanced glycation endproducts interacting with their endothelial receptor induce expression of vascular cell adhesion molecule-1 (VCAM-1) in cultured human endothelial cells and in mice. A potential mechanism for the accelerated vasculopathy of diabetes. J. Clin. Invest.,  1995, 96(3), 1395-1403.
[http://dx.doi.org/10.1172/JCI118175] [PMID: 7544803 ] 
[28] 
Chakravarthy, U.; Hayes, R.G.; Stitt, A.W.; McAuley, E.; Archer, D.B. Constitutive nitric oxide synthase expression in retinal vascular endothelial cells is suppressed by high glucose and advanced glycation end products. Diabetes,  1998, 47(6), 945-952.
[http://dx.doi.org/10.2337/diabetes.47.6.945] [PMID: 9604873 ] 
[29] 
Quehenberger, P.; Bierhaus, A.; Fasching, P.; Muellner, C.; Klevesath, M.; Hong, M.; Stier, G.; Sattler, M.; Schleicher, E.; Speiser, W.; Nawroth, P.P. Endothelin 1 transcription is controlled by nuclear factor-kappaB in AGE-stimulated cultured endothelial cells. Diabetes,  2000, 49(9), 1561-1570.
[http://dx.doi.org/10.2337/diabetes.49.9.1561] [PMID: 10969841 ] 
[30] 
Matsubara, M.; Hayashi, N.; Jing, T.; Titani, K. Regulation of endothelial nitric oxide synthase by protein kinase C. J. Biochem.,  2003, 133(6), 773-781.
[http://dx.doi.org/10.1093/jb/mvg099] [PMID: 12869534 ] 
[31] 
Inoguchi, T.; Li, P.; Umeda, F.; Yu, H.Y.; Kakimoto, M.; Imamura, M.; Aoki, T.; Etoh, T.; Hashimoto, T.; Naruse, M.; Sano, H.; Utsumi, H.; Nawata, H. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C--dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes,  2000, 49(11), 1939-1945.
[http://dx.doi.org/10.2337/diabetes.49.11.1939] [PMID: 11078463 ] 
[32] 
Ogita, H.; Liao, J. Endothelial function and oxidative stress. Endothelium,  2004, 11(2), 123-132.
[http://dx.doi.org/10.1080/10623320490482664] [PMID: 15370071 ] 
[33] 
Bauersachs, J.; Widder, J.D. Tetrahydrobiopterin, endothelial nitric oxide synthase, and mitochondrial function in the heart. Hypertension,  2009, 53(6), 907-908.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.109.130435] [PMID: 19398653 ] 
[34] 
Rubio-Guerra, A.F.; Vargas-Robles, H.; Ramos-Brizuela, L.M.; Escalante-Acosta, B.A. Is tetrahydrobiopterin a therapeutic option in diabetic hypertensive patients? Integr. Blood Press. Control,  2010, 3, 125-132.
[http://dx.doi.org/10.2147/IBPC.S7479] [PMID: 21949628 ] 
[35] 
Loader, J.; Montero, D.; Lorenzen, C.; Watts, R.; Méziat, C.; Reboul, C.; Stewart, S.; Walther, G. Acute hyperglycemia impairs vascular function in healthy and cardiometabolic diseased subjects: systematic review and meta-analysis. Arterioscler. Thromb. Vasc. Biol.,  2015, 35(9), 2060-2072.
[http://dx.doi.org/10.1161/ATVBAHA.115.305530] [PMID: 26112007 ] 
[36] 
Joy, N.G.; Perkins, J.M.; Mikeladze, M.; Younk, L.; Tate, D.B.; Davis, S.N. Comparative effects of acute hypoglycemia and hyperglycemia on pro-atherothrombotic biomarkers and endothelial function in non-diabetic humans. J. Diabetes Complications,  2016, 30(7), 1275-1281.
[http://dx.doi.org/10.1016/j.jdiacomp.2016.06.030] [PMID: 27445005 ] 
[37] 
Fonseca, V.A. The effects of insulin on the endothelium. Endocrinol. Metab. Clin. North Am.,  2007, 36(Suppl. 2), 20-26.
[http://dx.doi.org/10.1016/S0889-8529(07)80009-0] [PMID: 18407031 ] 
[38] 
King, G.L.; Park, K.; Li, Q. Selective insulin resistance and the development of cardiovascular diseases in diabetes: The 2015 Edwin Bierman award lecture. Diabetes,  2016, 65(6), 1462-1471.
[http://dx.doi.org/10.2337/db16-0152] [PMID: 27222390 ] 
[39] 
Ward, C.W.; Gough, K.H.; Rashke, M.; Wan, S.S.; Tribbick, G.; Wang, J. Systematic mapping of potential binding sites for Shc and Grb2 SH2 domains on insulin receptor substrate-1 and the receptors for insulin, epidermal growth factor, platelet-derived growth factor, and fibroblast growth factor. J. Biol. Chem.,  1996, 271(10), 5603-5609.
[http://dx.doi.org/10.1074/jbc.271.10.5603] [PMID: 8621421 ] 
[40] 
Cusi, K.; Maezono, K.; Osman, A.; Pendergrass, M.; Patti, M.E.; Pratipanawatr, T.; DeFronzo, R.A.; Kahn, C.R.; Mandarino, L.J. Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle. J. Clin. Invest.,  2000, 105(3), 311-320.
[http://dx.doi.org/10.1172/JCI7535] [PMID: 10675357 ] 
[41] 
Kim, Y.B.; Nikoulina, S.E.; Ciaraldi, T.P.; Henry, R.R.; Kahn, B.B. Normal insulin-dependent activation of Akt/protein kinase B, with diminished activation of phosphoinositide 3-kinase, in muscle in type 2 diabetes. J. Clin. Invest.,  1999, 104(6), 733-741.
[http://dx.doi.org/10.1172/JCI6928] [PMID:  10491408] 
[42] 
Jiang, Z.Y.; Lin, Y.W.; Clemont, A.; Feener, E.P.; Hein, K.D.; Igarashi, M.; Yamauchi, T.; White, M.F.; King, G.L. Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats. J. Clin. Invest.,  1999, 104(4), 447-457.
[http://dx.doi.org/10.1172/JCI5971] [PMID:  10449437] 
[43] 
Janus, A.; Szahidewicz-Krupska, E.; Mazur, G.; Doroszko, A. Insulin resistance and endothelial dysfunction constitute a common therapeutic target in cardiometabolic disorders. Mediators Inflamm.,  2016, 20163634948
[http://dx.doi.org/10.1155/2016/3634948] [PMID:  27413253] 
[44] 
Engin, A.B. What Is Lipotoxicity? Adv. Exp. Med. Biol.,  2017, 960, 197-220.
[http://dx.doi.org/10.1007/978-3-319-48382-5_8] [PMID: 28585200] 
[45] 
Ghosh, A.; Gao, L.; Thakur, A.; Siu, P.M.; Lai, C.W.K. Role of free fatty acids in endothelial dysfunction. J. Biomed. Sci.,  2017, 24(1), 50.
[http://dx.doi.org/10.1186/s12929-017-0357-5] [PMID:  28750629  ] 
[46] 
Symons, J.D.; Abel, E.D. Lipotoxicity contributes to endothelial dysfunction: a focus on the contribution from ceramide. Rev. Endocr. Metab. Disord.,  2013, 14(1), 59-68.
[http://dx.doi.org/10.1007/s11154-012-9235-3] [PMID: 23292334  ] 
[47] 
Tang, Y.; Li, G. Chronic exposure to high fatty acids impedes receptor agonist-induced nitric oxide production and increments of cytosolic Ca2+ levels in endothelial cells. J. Mol. Endocrinol.,  2011, 47(3), 315-326.
[http://dx.doi.org/10.1530/JME-11-0082] [PMID:  21994216] 
[48] 
Sena, C.M.; Pereira, A.M.; Seiça, R. Endothelial dysfunction - a major mediator of diabetic vascular disease. Biochim. Biophys. Acta,  2013, 1832(12), 2216-2231.
[http://dx.doi.org/10.1016/j.bbadis.2013.08.006] [PMID: 23994612  ] 
[49] 
Wu, M.Y.; Yiang, G.T.; Lai, T.T.; Li, C.J. The oxidative stress and mitochondrial dysfunction during the pathogenesis of diabetic retinopathy. Oxid. Med. Cell. Longev.,  2018, 20183420187
[http://dx.doi.org/10.1155/2018/3420187] [PMID: 30254714 ] 
[50] 
Siasos, G.; Gouliopoulos, N.; Moschos, M.M.; Oikonomou, E.; Kollia, C.; Konsola, T.; Athanasiou, D.; Siasou, G.; Mourouzis, K.; Zisimos, K.; Papavassiliou, A.G.; Stefanadis, C.; Tousoulis, D. Role of endothelial dysfunction and arterial stiffness in the development of diabetic retinopathy. Diabetes Care,  2015, 38(1), e9-e10.
[http://dx.doi.org/10.2337/dc14-1741] [PMID: 25538324 ] 
[51] 
Yun, J.S.; Ko, S.H.; Kim, J.H.; Moon, K.W.; Park, Y.M.; Yoo, K.D.; Ahn, Y.B. Diabetic retinopathy and endothelial dysfunction in patients with type 2 diabetes mellitus. Diabetes Metab. J.,  2013, 37(4), 262-269.
[http://dx.doi.org/10.4093/dmj.2013.37.4.262] [PMID:  23991404] 
[52] 
Malecki, M.T.; Osmenda, G.; Walus-Miarka, M.; Skupien, J.; Cyganek, K.; Mirkiewicz-Sieradzka, B. damek-Guzik, T.A.; Guzik, T.J.; Sieradzki, J. Retinopathy in type 2 diabetes mellitus is associated with increased intima-media thickness and endothelial dysfunction. Eur. J. Clin. Invest.,  2008, 38(12), 925-930.
[http://dx.doi.org/10.1111/j.1365-2362.2008.02051.x] [PMID: 19021717 ] 
[53] 
Nguyen, T.T.; Shaw, J.E.; Robinson, C.; Kawasaki, R.; Wang, J.J.; Kreis, A.J.; Wong, T.Y. Diabetic retinopathy is related to both endothelium-dependent and -independent responses of skin microvascular flow. Diabetes Care,  2011, 34(6), 1389-1393.
[http://dx.doi.org/10.2337/dc10-1985] [PMID: 21515845 ] 
[54] 
Sogawa, K.; Nagaoka, T.; Tanano, I.; Tani, T.; Omae, T.; Nakabayashi, S.; Ishibazawa, A.; Takahashi, A.; Yoshida, A. Association between diabetic retinopathy and flow-mediated vasodilation in type 2 DM. Curr. Eye Res.,  2012, 37(5), 446-451.
[http://dx.doi.org/10.3109/02713683.2012.654883] [PMID: 22510012 ] 
[55] 
Lim, L.S.; Ling, L.H.; Cheung, C.M.; Ong, P.G.; Gong, L.; Tai, E.S.; Mathur, R.; Wong, D.; Foulds, W.; Wong, T.Y. Relationship of systemic endothelial function and peripheral arterial stiffness with diabetic retinopathy. Br. J. Ophthalmol.,  2015, 99(6), 837-841.
[http://dx.doi.org/10.1136/bjophthalmol-2014-306075] [PMID: 25488949 ] 
[56] 
Olson, J.A.; Whitelaw, C.M.; McHardy, K.C.; Pearson, D.W.; Forrester, J.V. Soluble leucocyte adhesion molecules in diabetic retinopathy stimulate retinal capillary endothelial cell migration. Diabetologia,  1997, 40(10), 1166-1171.
[http://dx.doi.org/10.1007/s001250050802] [PMID: 9349597  ] 
[57] 
van Hecke, M.V.; Dekker, J.M.; Nijpels, G.; Moll, A.C.; Heine, R.J.; Bouter, L.M.; Polak, B.C.; Stehouwer, C.D. Inflammation and endothelial dysfunction are associated with retinopathy: the Hoorn Study. Diabetologia,  2005, 48(7), 1300-1306.
[http://dx.doi.org/10.1007/s00125-005-1799-y] [PMID: 15918015  ] 
[58] 
Oku, H.; Kida, T.; Sugiyama, T.; Hamada, J.; Sato, B.; Ikeda, T. Possible involvement of endothelin-1 and nitric oxide in the pathogenesis of proliferative diabetic retinopathy. Retina,  2001, 21(6), 647-651.
[http://dx.doi.org/10.1097/00006982-200112000-00013] [PMID: 11756889  ] 
[59] 
Sorrentino, F.S.; Matteini, S.; Bonifazzi, C.; Sebastiani, A.; Parmeggiani, F. Diabetic retinopathy and endothelin system: microangiopathy versus endothelial dysfunction. Eye (Lond.),  2018, 32(7), 1157-1163.
[http://dx.doi.org/10.1038/s41433-018-0032-4] [PMID: 29520046 ] 
[60] 
Spijkerman, A.M.; Gall, M.A.; Tarnow, L.; Twisk, J.W.; Lauritzen, E.; Lund-Andersen, H.; Emeis, J.; Parving, H.H.; Stehouwer, C.D. Endothelial dysfunction and low-grade inflammation and the progression of retinopathy in Type 2 diabetes. Diabet. Med.,  2007, 24(9), 969-976.
[http://dx.doi.org/10.1111/j.1464-5491.2007.02217.x] [PMID: 17593241 ] 
[61] 
Sasongko, M.B.; Wong, T.Y.; Jenkins, A.J.; Nguyen, T.T.; Shaw, J.E.; Wang, J.J. Circulating markers of inflammation and endothelial function, and their relationship to diabetic retinopathy. Diabet. Med.,  2015, 32(5), 686-691.
[http://dx.doi.org/10.1111/dme.12640] [PMID: 25407692 ] 
[62] 
Uğurlu, N.; Gerceker, S.; Yülek, F.; Ugurlu, B.; Sarı, C.; Baran, P.; Çağil, N. The levels of the circulating cellular adhesion molecules ICAM-1, VCAM-1 and endothelin-1 and the flow-mediated vasodilatation values in patients with type 1 diabetes mellitus with early-stage diabetic retinopathy. Intern. Med.,  2013, 52(19), 2173-2178.
[http://dx.doi.org/10.2169/internalmedicine.52.8572] [PMID: 24088748  ] 
[63] 
Rajab, H.A.; Baker, N.L.; Hunt, K.J.; Klein, R.; Cleary, P.A.; Lachin, J.; Virella, G.; Lopes-Virella, M.F. DCCT/EDIC Group of Investigators. The predictive role of markers of Inflammation and endothelial dysfunction on the course of diabetic retinopathy in type 1 diabetes. J. Diabetes Complications,  2015, 29(1), 108-114.
[http://dx.doi.org/10.1016/j.jdiacomp.2014.08.004] [PMID: 25441222 ] 
[64] 
Lois, N.; McCarter, R.V.; O’Neill, C.; Medina, R.J.; Stitt, A.W. Endothelial progenitor cells in diabetic retinopathy. Front. Endocrinol. (Lausanne),  2014, 5, 44.
[http://dx.doi.org/10.3389/fendo.2014.00044] [PMID: 24782825 ] 
[65] 
Yu, C.G.; Zhang, N.; Yuan, S.S.; Ma, Y.; Yang, L.Y.; Feng, Y.M.; Zhao, D. Endothelial progenitor cells in diabetic microvascular complications: friends or foes? Stem Cells Int.,  2016, 20161803989
[http://dx.doi.org/10.1155/2016/1803989] [PMID:  27313624] 
[66] 
Gilbert, R.E. The endothelium in diabetic nephropathy. Curr. Atheroscler. Rep.,  2014, 16(5), 410.
[http://dx.doi.org/10.1007/s11883-014-0410-8] [PMID: 24623181 ] 
[67] 
Leung, W.K.; Gao, L.; Siu, P.M.; Lai, C.W. Diabetic nephropathy and endothelial dysfunction: Current and future therapies, and emerging of vascular imaging for preclinical renal-kinetic study. Life Sci.,  2016, 166, 121-130.
[http://dx.doi.org/10.1016/j.lfs.2016.10.015] [PMID: 27765534 ] 
[68] 
El-Din Bessa, S.S.; Hamdy, S.M. Impact of nitric oxide synthase Glu298Asp polymorphism on the development of end-stage renal disease in type 2 diabetic Egyptian patients. Ren. Fail.,  2011, 33(9), 878-884.
[http://dx.doi.org/10.3109/0886022X.2011.605978] [PMID: 21854353  ] 
[69] 
Yokoyama, H.; Sone, H.; Saito, K.; Yamada, D.; Honjo, J.; Haneda, M. Flow-mediated dilation is associated with microalbuminuria independent of cardiovascular risk factors in type 2 diabetes - interrelations with arterial thickness and stiffness. J. Atheroscler. Thromb.,  2011, 18(9), 744-752.
[http://dx.doi.org/10.5551/jat.7526] [PMID: 21597231 ] 
[70] 
Stehouwer, C.D.; Henry, R.M.; Dekker, J.M.; Nijpels, G.; Heine, R.J.; Bouter, L.M. Microalbuminuria is associated with impaired brachial artery, flow-mediated vasodilation in elderly individuals without and with diabetes: further evidence for a link between microalbuminuria and endothelial dysfunction--the Hoorn Study. Kidney Int. Suppl.,  2004, (92), S42-S44.
[http://dx.doi.org/10.1111/j.1523-1755.2004.09211.x] [PMID: 15485416 ] 
[71] 
Silva, A.M.; Schaan, B.D.; Signori, L.U.; Plentz, R.D.; Moreno, H., Jr; Bertoluci, M.C.; Irigoyen, M.C. Microalbuminuria is associated with impaired arterial and venous endothelium-dependent vasodilation in patients with Type 2 diabetes. J. Endocrinol. Invest.,  2010, 33(10), 696-700.
[http://dx.doi.org/10.1007/BF03346672] [PMID: 20354354 ] 
[72] 
Ito, H.; Nakashima, M.; Meguro, K.; Furukawa, H.; Yamashita, H.; Takaki, A.; Yukawa, C.; Omoto, T.; Shinozaki, M.; Nishio, S.; Abe, M.; Antoku, S.; Mifune, M.; Togane, M. Flow mediated dilatation is reduced with the progressive stages of glomerular filtration rate and albuminuria in type 2 diabetic patients without coronary heart disease. J. Diabetes Res.,  2015, 2015728127
[http://dx.doi.org/10.1155/2015/728127] [PMID: 26064988 ] 
[73] 
Naka, K.K.; Papathanassiou, K.; Bechlioulis, A.; Kazakos, N.; Pappas, K.; Tigas, S.; Makriyiannis, D.; Tsatsoulis, A.; Michalis, L.K. Determinants of vascular function in patients with type 2 diabetes. Cardiovasc. Diabetol.,  2012, 11, 127.
[http://dx.doi.org/10.1186/1475-2840-11-127] [PMID: 23062182  ] 
[74] 
Marra, M.; Marchegiani, F.; Ceriello, A.; Sirolla, C.; Boemi, M.; Franceschi, C.; Spazzafumo, L.; Testa, I.; Bonfigli, A.R.; Cucchi, M.; Testa, R. Chronic renal impairment and DDAH2-1151 A/C polymorphism determine ADMA levels in type 2 diabetic subjects. Nephrol. Dial. Transplant.,  2013, 28(4), 964-971.
[http://dx.doi.org/10.1093/ndt/gfs516] [PMID:  23129820] 
[75] 
Stehouwer, C.D.; Gall, M.A.; Twisk, J.W.; Knudsen, E.; Emeis, J.J.; Parving, H.H. Increased urinary albumin excretion, endothelial dysfunction, and chronic low-grade inflammation in type 2 diabetes: progressive, interrelated, and independently associated with risk of death. Diabetes,  2002, 51(4), 1157-1165.
[http://dx.doi.org/10.2337/diabetes.51.4.1157] [PMID: 11916939 ] 
[76] 
Zanatta, C.M.; Gerchman, F.; Burttet, L.; Nabinger, G.; Jacques-Silva, M.C.; Canani, L.H.; Gross, J.L. Endothelin-1 levels and albuminuria in patients with type 2 diabetes mellitus. Diabetes Res. Clin. Pract.,  2008, 80(2), 299-304.
[http://dx.doi.org/10.1016/j.diabres.2007.12.024] [PMID: 18346810 ] 
[77] 
Bruno, C.M.; Meli, S.; Marcinno, M.; Ierna, D.; Sciacca, C.; Neri, S. Plasma endothelin-1 levels and albumin excretion rate in normotensive, microalbuminuric type 2 diabetic patients. J. Biol. Regul. Homeost. Agents,  2002, 16(2), 114-117.
[PMID: 12144123 ] 
[78] 
Zeravica, R.; Ilincic, B.; Cabarkapa, V.; Sakac, V.; Crnobrnja, V.; Stosic, Z. Plasma endothelin- 1 levels and albuminuria in patients with type 2 diabetes mellitus. Med. Pregl.,  2016, 69(5-6), 140-145.
[http://dx.doi.org/10.2298/MPNS1606140Z] [PMID: 29693840 ] 
[79] 
Bahlmann, F.H.; De Groot, K.; Spandau, J.M.; Landry, A.L.; Hertel, B.; Duckert, T.; Boehm, S.M.; Menne, J.; Haller, H.; Fliser, D. Erythropoietin regulates endothelial progenitor cells. Blood,  2004, 103(3), 921-926.
[http://dx.doi.org/10.1182/blood-2003-04-1284] [PMID: 14525788 ] 
[80] 
Makino, H.; Okada, S.; Nagumo, A.; Sugisawa, T.; Miyamoto, Y.; Kishimoto, I.; Kikuchi-Taura, A.; Soma, T.; Taguchi, A.; Yoshimasa, Y. Decreased circulating CD34+ cells are associated with progression of diabetic nephropathy. Diabet. Med.,  2009, 26(2), 171-173.
[http://dx.doi.org/10.1111/j.1464-5491.2008.02638.x] [PMID: 19236621 ] 
[81] 
Harmer, J.A.; Keech, A.C.; Veillard, A.S.; Skilton, M.R.; Marwick, T.H.; Watts, G.F.; Meredith, I.T.; Celermajer, D.S.; Investigators, F.V.S. FIELD Vascular Study Investigators. Cigarette smoking and albuminuria are associated with impaired arterial smooth muscle function in patients with type 2 diabetes mellitus: a FIELD substudy. Diabetes Res. Clin. Pract.,  2014, 106(2), 328-336.
[http://dx.doi.org/10.1016/j.diabres.2014.08.029] [PMID:  25301035 ] 
[82] 
Roustit, M.; Loader, J.; Deusenbery, C.; Baltzis, D.; Veves, A. Endothelial dysfunction as a link between cardiovascular risk factors and peripheral neuropathy in diabetes. J. Clin. Endocrinol. Metab.,  2016, 101(9), 3401-3408.
[http://dx.doi.org/10.1210/jc.2016-2030] [PMID:  27399351 ] 
[83] 
Hafer-Macko, C.E.; Ivey, F.M.; Sorkin, J.D.; Macko, R.F. Microvascular tissue plasminogen activator is reduced in diabetic neuropathy. Neurology,  2007, 69(3), 268-274.
[http://dx.doi.org/10.1212/01.wnl.0000266391.20707.83] [PMID: 17636064 ] 
[84] 
Eleftheriadou, I.; Tentolouris, A.; Grigoropoulou, P.; Tsilingiris, D.; Anastasiou, I.; Kokkinos, A.; Perrea, D.; Katsilambros, N.; Tentolouris, N. The association of diabetic microvascular and macrovascular disease with cutaneous circulation in patients with type 2 diabetes mellitus. J. Diabetes Complications, 2018.
[PMID: 30446479 ] 
[85] 
Fakhrzadeh, H.; Yamini-Sharif, A.; Sharifi, F.; Tajalizadekhoob, Y.; Mirarefin, M.; Mohammadzadeh, M.; Sadeghian, S.; Badamchizadeh, Z.; Larijani, B. Cardiac autonomic neuropathy measured by heart rate variability and markers of subclinical atherosclerosis in early type 2 diabetes. ISRN Endocrinol.,  2012, 2012168264
[http://dx.doi.org/10.5402/2012/168264] [PMID: 23259073 ] 
[86] 
Tiftikcioglu, B.I.; Bilgin, S.; Duksal, T.; Kose, S.; Zorlu, Y. Autonomic neuropathy and endothelial dysfunction in patients with impaired glucose tolerance or type 2 diabetes mellitus. Medicine (Baltimore),  2016, 95(14)e3340
[http://dx.doi.org/10.1097/MD.0000000000003340] [PMID: 27057914 ] 
[87] 
Antonopoulos, A.S.; Siasos, G.; Konsola, T.; Oikonomou, E.; Tentolouris, N.; Kollia, C.; Gouliopoulos, N.; Zografos, T.; Papavassiliou, A.G.; Tousoulis, D. Arterial wall elastic properties and endothelial dysfunction in the diabetic foot syndrome in patients with type 2 diabetes. Diabetes Care,  2015, 38(11), e180-e181.
[http://dx.doi.org/10.2337/dc15-1042] [PMID: 26294663 ] 
[88] 
Baltzis, D.; Eleftheriadou, I.; Veves, A. Pathogenesis and treatment of impaired wound healing in diabetes mellitus: new insights. Adv. Ther.,  2014, 31(8), 817-836.
[http://dx.doi.org/10.1007/s12325-014-0140-x] [PMID: 25069580 ] 
[89] 
Edmonds, M.E.; Bodansky, H.J.; Boulton, A.J.M.; Chadwick, P.J.; Dang, C.N.; D’Costa, R.; Johnston, A.; Kennon, B.; Leese, G.; Rajbhandari, S.M.; Serena, T.E.; Young, M.J.; Stewart, J.E.; Tucker, A.T.; Carter, M.J. Multicenter, randomized controlled, observer-blinded study of a nitric oxide generating treatment in foot ulcers of patients with diabetes-ProNOx1 study. Wound Repair Regen.,  2018, 26(2), 228-237.
[http://dx.doi.org/10.1111/wrr.12630] [PMID: 29617058 ] 
[90] 
Castela, Â.; Costa, C. Molecular mechanisms associated with diabetic endothelial-erectile dysfunction. Nat. Rev. Urol.,  2016, 13(5), 266-274.
[http://dx.doi.org/10.1038/nrurol.2016.23] [PMID: 26878803 ] 
[91] 
Murata, M.; Tamemoto, H.; Otani, T.; Jinbo, S.; Ikeda, N.; Kawakami, M.; Ishikawa, S.E. Endothelial impairment and bone marrow-derived CD34(+)/133(+) cells in diabetic patients with erectile dysfunction. J. Diabetes Investig.,  2012, 3(6), 526-533.
[http://dx.doi.org/10.1111/j.2040-1124.2012.00230.x] [PMID: 24843618 ] 
[92] 
Araña, Rosaínz. Mde.J.; Ojeda, M.O.; Acosta, J.R.; Elías-Calles, L.C.; González, N.O.; Herrera, O.T.; García Álvarez, C.T.; Rodríguez, E.M.; Báez, M.E.; Seijas, E.A.; Valdés, R.F. Imbalanced low-grade inflammation and endothelial activation in patients with type 2 diabetes mellitus and erectile dysfunction. J. Sex. Med.,  2011, 8(7), 2017-2030.
[http://dx.doi.org/10.1111/j.1743-6109.2011.02277.x] [PMID: 21554550 ] 
[93] 
Maiorino, M.I.; Bellastella, G.; Petrizzo, M.; Della Volpe, E.; Orlando, R.; Giugliano, D.; Esposito, K. Circulating endothelial progenitor cells in type 1 diabetic patients with erectile dysfunction. Endocrine,  2015, 49(2), 415-421.
[http://dx.doi.org/10.1007/s12020-014-0478-5] [PMID: 25411101 ] 
[94] 
Osondu, C.U.; Vo, B.; Oni, E.T.; Blaha, M.J.; Veledar, E.; Feldman, T.; Agatston, A.S.; Nasir, K.; Aneni, E.C. The relationship of erectile dysfunction and subclinical cardiovascular disease: A systematic review and meta-analysis. Vasc. Med.,  2018, 23(1), 9-20.
[http://dx.doi.org/10.1177/1358863X17725809] [PMID: 29243995 ] 
[95] 
Tentolouris, A.; Eleftheriadou, I.; Athanasakis, K.; Kyriopoulos, J.; Tsilimigras, D.I.; Grigoropoulou, P.; Doupis, J.; Tentolouris, N. Prevalence of diabetes mellitus as well as
cardiac and other main comorbidities in a representative
sample of the adult Greek population in comparison with the
general population. Hellenic J. Cardiol.,  2018, S1109-
9666(18)30038-1 Epub ahead of print.
[http://dx.doi.org/10.1016/j.hjc.2018.04.008] [PMID: 29729413 ] 
[96] 
Gu, K.; Cowie, C.C.; Harris, M.I. Mortality in adults with and without diabetes in a national cohort of the U.S. population, 1971-1993. Diabetes Care,  1998, 21(7), 1138-1145.
[http://dx.doi.org/10.2337/diacare.21.7.1138] [PMID: 9653609 ] 
[97] 
Gimbrone, M.A. Jr.; García-Cardeña, G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ. Res.,  2016, 118(4), 620-636.
[http://dx.doi.org/10.1161/CIRCRESAHA.115.306301] [PMID: 26892962 ] 
[98] 
Ylä-Herttuala, S.; Bentzon, J.F.; Daemen, M.; Falk, E.; Garcia-Garcia, H.M.; Herrmann, J.; Hoefer, I.; Jauhiainen, S.; Jukema, J.W.; Krams, R.; Kwak, B.R.; Marx, N.; Naruszewicz, M.; Newby, A.; Pasterkamp, G.; Serruys, P.W.; Waltenberger, J.; Weber, C.; Tokgözoglu, L.; Atherosclerosis, E.S.C.W.G.; Vascular, B. ESC working group of atherosclerosis and vascular biology. stabilization of atherosclerotic plaques: an update. Eur. Heart J.,  2013, 34(42), 3251-3258.
[http://dx.doi.org/10.1093/eurheartj/eht301] [PMID:  23966311 ] 
[99] 
Reyes-Soffer, G.; Holleran, S.; Di Tullio, M.R.; Homma, S.; Boden-Albala, B.; Ramakrishnan, R.; Elkind, M.S.; Sacco, R.L.; Ginsberg, H.N. Endothelial function in individuals with coronary artery disease with and without type 2 diabetes mellitus. Metabolism,  2010, 59(9), 1365-1371.
[http://dx.doi.org/10.1016/j.metabol.2009.12.023] [PMID: 20102776 ] 
[100] 
Simova, I.I.; Denchev, S.V.; Dimitrov, S.I.; Ivanova, R. Endothelial function in patients with and without diabetes mellitus with different degrees of coronary artery stenosis. J. Clin. Ultrasound,  2009, 37(1), 35-39.
[http://dx.doi.org/10.1002/jcu.20532] [PMID: 18819073 ] 
[101] 
Djaberi, R.; Roodt, Jo.; Schuijf, J.D.; Rabelink, T.J.; de Koning, E.J.; Pereira, A.M.; Stokkel, M.P.; Smit, J.W.; Bax, J.J.; Jukema, J.W. Endothelial dysfunction in diabetic patients with abnormal myocardial perfusion in the absence of epicardial obstructive coronary artery disease. J. Nucl. Med.,  2009, 50(12), 1980-1986.
[http://dx.doi.org/10.2967/jnumed.109.065193] [PMID: 19910438 ] 
[102] 
Natarajan, A.; Marshall, S.M.; Kesteven, P.J.; McComb, J.M.; Rutter, M.K. Impact of biomarkers for endothelial dysfunction and procoagulant state on 10-year cardiovascular risk in Type 2 diabetes. Diabet. Med.,  2011, 28(10), 1201-1205.
[http://dx.doi.org/10.1111/j.1464-5491.2011.03311.x] [PMID:  21480978 ] 
[103] 
von Scholten, B.J.; Reinhard, H.; Hansen, T.W.; Schalkwijk, C.G.; Stehouwer, C.; Parving, H.H.; Jacobsen, P.K.; Rossing, P. Markers of inflammation and endothelial dysfunction are associated with incident cardiovascular disease, all-cause mortality, and progression of coronary calcification in type 2 diabetic patients with microalbuminuria. J. Diabetes Complications,  2016, 30(2), 248-255.
[http://dx.doi.org/10.1016/j.jdiacomp.2015.11.005] [PMID: 26651261 ] 
[104] 
Fadini, G.P.; Sartore, S.; Albiero, M.; Baesso, I.; Murphy, E.; Menegolo, M.; Grego, F.; Vigili de Kreutzenberg, S.; Tiengo, A.; Agostini, C.; Avogaro, A. Number and function of endothelial progenitor cells as a marker of severity for diabetic vasculopathy. Arterioscler. Thromb. Vasc. Biol.,  2006, 26(9), 2140-2146.
[http://dx.doi.org/10.1161/01.ATV.0000237750.44469.88] [PMID: 16857948 ] 
[105] 
Matsuzawa, Y.; Kwon, T.G.; Lennon, R.J.; Lerman, L.O.; Lerman, A. Prognostic value of flow-mediated vasodilation in brachial artery and fingertip artery for cardiovascular events: a systematic review and meta-analysis. J. Am. Heart Assoc.,  2015, 4(11)e002270
[http://dx.doi.org/10.1161/JAHA.115.002270] [PMID: 26567372 ] 
[106] 
Davies, M.J.; D’Alessio, D.A.; Fradkin, J.; Kernan, W.N.; Mathieu, C.; Mingrone, G.; Rossing, P.; Tsapas, A.; Wexler, D.J.; Buse, J.B. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care,  2018, 41(12), 2669-2701.
[http://dx.doi.org/10.2337/dci18-0033] [PMID: 30291106 ] 
[107] 
Eleftheriadou, I.; Grigoropoulou, P.; Liberopoulos, E.; Liatis, S.; Kokkinos, A.; Tentolouris, N. Update on cardiovascular effects of older and newer anti-diabetic medications. Curr. Med. Chem.,  2018, 25(13), 1549-1566.
[http://dx.doi.org/10.2174/0929867324666170530075533] [PMID: 28554326 ] 
[108] 
Shigiyama, F.; Kumashiro, N.; Miyagi, M.; Ikehara, K.; Kanda, E.; Uchino, H.; Hirose, T. Effectiveness of dapagliflozin on vascular endothelial function and glycemic control in patients with early-stage type 2 diabetes mellitus: DEFENCE study. Cardiovasc. Diabetol.,  2017, 16(1), 84.
[http://dx.doi.org/10.1186/s12933-017-0564-0] [PMID: 28683796 ] 
[109] 
Li, F.; Chen, J.; Leng, F.; Lu, Z.; Ling, Y. Effect of saxagliptin on circulating endothelial progenitor cells and endothelial function in newly diagnosed type 2 diabetic patients. Exp. Clin. Endocrinol. Diabetes,  2017, 125(6), 400-407.
[http://dx.doi.org/10.1055/s-0042-124421] [PMID: 28407661 ] 
[110] 
Pitocco, D.; Zaccardi, F.; Tarzia, P.; Milo, M.; Scavone, G.; Rizzo, P.; Pagliaccia, F.; Nerla, R.; Di Franco, A.; Manto, A.; Rocca, B.; Lanza, G.A.; Crea, F.; Ghirlanda, G. Metformin improves endothelial function in type 1 diabetic subjects: a pilot, placebo-controlled randomized study. Diabetes Obes. Metab.,  2013, 15(5), 427-431.
[http://dx.doi.org/10.1111/dom.12041] [PMID:  23167274  ] 
[111] 
Naka, K.K.; Papathanassiou, K.; Bechlioulis, A.; Pappas, K.; Kazakos, N.; Kanioglou, C.; Kostoula, A.; Vezyraki, P.; Makriyiannis, D.; Tsatsoulis, A.; Michalis, L.K. Effects of pioglitazone and metformin on vascular endothelial function in patients with type 2 diabetes treated with sulfonylureas. Diab. Vasc. Dis. Res.,  2012, 9(1), 52-58.
[http://dx.doi.org/10.1177/1479164111424515] [PMID: 22049096 ] 
[112] 
Kitao, N.; Miyoshi, H.; Furumoto, T.; Ono, K.; Nomoto, H.; Miya, A.; Yamamoto, C.; Inoue, A.; Tsuchida, K.; Manda, N.; Kurihara, Y.; Aoki, S.; Nakamura, A.; Atsumi, T.; Group, S.S. SAIS Study Group. The effects of vildagliptin compared with metformin on vascular endothelial function and metabolic parameters: a randomized, controlled trial (Sapporo Athero-Incretin Study 3). Cardiovasc. Diabetol.,  2017, 16(1), 125.
[http://dx.doi.org/10.1186/s12933-017-0607-6] [PMID:  29017497] 
[113] 
Lambadiari, V.; Pavlidis, G.; Kousathana, F.; Varoudi, M.; Vlastos, D.; Maratou, E.; Georgiou, D.; Andreadou, I.; Parissis, J.; Triantafyllidi, H.; Lekakis, J.; Iliodromitis, E.; Dimitriadis, G.; Ikonomidis, I. Effects of 6-month treatment with the glucagon like peptide-1 analogue liraglutide on arterial stiffness, left ventricular myocardial deformation and oxidative stress in subjects with newly diagnosed type 2 diabetes. Cardiovasc. Diabetol.,  2018, 17(1), 8.
[http://dx.doi.org/10.1186/s12933-017-0646-z] [PMID: 29310645 ] 
[114] 
Shigiyama, F.; Kumashiro, N.; Miyagi, M.; Iga, R.; Kobayashi, Y.; Kanda, E.; Uchino, H.; Hirose, T. Linagliptin improves endothelial function in patients with type 2 diabetes: A randomized study of linagliptin effectiveness on endothelial function. J. Diabetes Investig.,  2017, 8(3), 330-340.
[http://dx.doi.org/10.1111/jdi.12587] [PMID:  27868359] 
[115] 
de Jager, J.; Kooy, A.; Schalkwijk, C.; van der Kolk, J.; Lehert, P.; Bets, D.; Wulffelé, M.G.; Donker, A.J.; Stehouwer, C.D. Long-term effects of metformin on endothelial function in type 2 diabetes: a randomized controlled trial. J. Intern. Med.,  2014, 275(1), 59-70.
[http://dx.doi.org/10.1111/joim.12128] [PMID: 23981104 ] 
[116] 
Erem, C.; Ozbas, H.M.; Nuhoglu, I.; Deger, O.; Civan, N.; Ersoz, H.O. Comparison of effects of gliclazide, metformin and pioglitazone monotherapies on glycemic control and cardiovascular risk factors in patients with newly diagnosed uncontrolled type 2 diabetes mellitus. Exp. Clin. Endocrinol. Diabetes,  2014, 122(5), 295-302.
[http://dx.doi.org/10.1055/s-0034-1370989] [PMID: 24710641 ] 
[117] 
Fidan, E.; Onder Ersoz, H.; Yilmaz, M.; Yilmaz, H.; Kocak, M.; Karahan, C.; Erem, C. The effects of rosiglitazone and metformin on inflammation and endothelial dysfunction in patients with type 2 diabetes mellitus. Acta Diabetol.,  2011, 48(4), 297-302.
[http://dx.doi.org/10.1007/s00592-011-0276-y] [PMID: 21424914 ] 
[118] 
Lund, S.S.; Tarnow, L.; Stehouwer, C.D.; Schalkwijk, C.G.; Teerlink, T.; Gram, J.; Winther, K.; Frandsen, M.; Smidt, U.M.; Pedersen, O.; Parving, H.H.; Vaag, A.A. Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes. Eur. J. Endocrinol.,  2008, 158(5), 631-641.
[http://dx.doi.org/10.1530/EJE-07-0815] [PMID: 18426821 ] 
[119] 
Skrha, J.; Prázný, M.; Hilgertová, J.; Kvasnicka, J.; Kalousová, M.; Zima, T. Oxidative stress and endothelium influenced by metformin in type 2 diabetes mellitus. Eur. J. Clin. Pharmacol.,  2007, 63(12), 1107-1114.
[http://dx.doi.org/10.1007/s00228-007-0378-1] [PMID: 17874238 ] 
[120] 
Arunachalam, G.; Samuel, S.M.; Marei, I.; Ding, H.; Triggle, C.R. Metformin modulates hyperglycaemia-induced endothelial senescence and apoptosis through SIRT1. Br. J. Pharmacol.,  2014, 171(2), 523-535.
[http://dx.doi.org/10.1111/bph.12496] [PMID: 24372553 ] 
[121] 
Kinaan, M.; Ding, H.; Triggle, C.R. Metformin: an old drug for the treatment of diabetes but a new drug for the protection of the endothelium. Med. Princ. Pract.,  2015, 24(5), 401-415.
[http://dx.doi.org/10.1159/000381643] [PMID: 26021280 ] 
[122] 
Hattori, Y.; Suzuki, K.; Hattori, S.; Kasai, K. Metformin inhibits cytokine-induced nuclear factor kappaB activation via AMP-activated protein kinase activation in vascular endothelial cells. Hypertension,  2006, 47(6), 1183-1188.
[http://dx.doi.org/10.1161/01.HYP.0000221429.94591.72] [PMID: 16636195 ] 
[123] 
Chen, L.L.; Yu, F.; Zeng, T.S.; Liao, Y.F.; Li, Y.M.; Ding, H.C. Effects of gliclazide on endothelial function in patients with newly diagnosed type 2 diabetes. Eur. J. Pharmacol.,  2011, 659(2-3), 296-301.
[http://dx.doi.org/10.1016/j.ejphar.2011.02.044] [PMID: 16636195 ] 
[124] 
Irace, C.; De Luca, S.; Shehaj, E.; Carallo, C.; Loprete, A.; Scavelli, F.; Gnasso, A. Exenatide improves endothelial function assessed by flow mediated dilation technique in subjects with type 2 diabetes: results from an observational research. Diab. Vasc. Dis. Res.,  2013, 10(1), 72-77.
[http://dx.doi.org/10.1177/1479164112449562] [PMID: 22732108 ] 
[125] 
Papathanassiou, K.; Naka, K.K.; Kazakos, N.; Kanioglou, C.; Makriyiannis, D.; Pappas, K.; Katsouras, C.S.; Liveris, K.; Kolettis, T.; Tsatsoulis, A.; Michalis, L.K. Pioglitazone vs glimepiride: Differential effects on vascular endothelial function in patients with type 2 diabetes. Atherosclerosis,  2009, 205(1), 221-226.
[http://dx.doi.org/10.1016/j.atherosclerosis.2008.11.027] [PMID: 19135671  ] 
[126] 
Nomoto, H.; Miyoshi, H.; Furumoto, T.; Oba, K.; Tsutsui, H.; Inoue, A.; Atsumi, T.; Manda, N.; Kurihara, Y.; Aoki, S.; Group, S.S. SAIS Study Group. A randomized controlled trial comparing the effects of sitagliptin and glimepiride on endothelial function and metabolic parameters: Sapporo Athero-Incretin Study 1 (SAIS1). PLoS One,  2016, 11(10)e0164255
[http://dx.doi.org/10.1371/journal.pone.0164255] [PMID: 27711199 ] 
[127] 
Jax, T.; Stirban, A.; Terjung, A.; Esmaeili, H.; Berk, A.; Thiemann, S.; Chilton, R.; von Eynatten, M.; Marx, N. A randomised, active- and placebo-controlled, three-period crossover trial to investigate short-term effects of the dipeptidyl peptidase-4 inhibitor linagliptin on macro- and microvascular endothelial function in type 2 diabetes. Cardiovasc. Diabetol.,  2017, 16(1), 13.
[http://dx.doi.org/10.1186/s12933-016-0493-3] [PMID: 28109295 ] 
[128] 
Nandy, D.; Johnson, C.; Basu, R.; Joyner, M.; Brett, J.; Svendsen, C.B.; Basu, A. The effect of liraglutide on endothelial function in patients with type 2 diabetes. Diab. Vasc. Dis. Res.,  2014, 11(6), 419-430.
[http://dx.doi.org/10.1177/1479164114547358] [PMID: 25212693 ] 
[129] 
Cosenso-Martin, L.N.; Giollo-Júnior, L.T.; Fernandes, L.A.B.; Cesarino, C.B.; Nakazone, M.A.; Machado, M.N.; Yugar-Toledo, J.C.; Vilela-Martin, J.F. Effect of vildagliptin versus glibenclamide on endothelial function and arterial stiffness in patients with type 2 diabetes and hypertension: a randomized controlled trial. Acta Diabetol.,  2018, 55(12), 1237-1245. Epub ahead of print
[http://dx.doi.org/10.1007/s00592-018-1204-1] [PMID: 30094725 ] 
[130] 
Dei Cas, A.; Spigoni, V.; Cito, M.; Aldigeri, R.; Ridolfi, V.; Marchesi, E.; Marina, M.; Derlindati, E.; Aloe, R.; Bonadonna, R.C.; Zavaroni, I. Vildagliptin, but not glibenclamide, increases circulating endothelial progenitor cell number: a 12-month randomized controlled trial in patients with type 2 diabetes. Cardiovasc. Diabetol.,  2017, 16(1), 27.
[http://dx.doi.org/10.1186/s12933-017-0503-0] [PMID: 28231835 ] 
[131] 
Abbink, E.J.; Pickkers, P.; Jansen van Rosendaal, A.; Lutterman, J.A.; Tack, C.J.; Russel, F.G.; Smits, P. Vascular effects of glibenclamide vs. glimepiride and metformin in Type 2 diabetic patients. Diabet. Med.,  2002, 19(2), 136-143.
[http://dx.doi.org/10.1046/j.1464-5491.2002.00663.x] [PMID: 11874430 ] 
[132] 
Jojima, T.; Suzuki, K.; Hirama, N.; Uchida, K.; Hattori, Y. Glimepiride upregulates eNOS activity and inhibits cytokine-induced NF-kappaB activation through a phosphoinoside 3-kinase-Akt-dependent pathway. Diabetes Obes. Metab.,  2009, 11(2), 143-149.
[http://dx.doi.org/10.1111/j.1463-1326.2008.00923.x] [PMID: 18564176 ] 
[133] 
Scott, N.A.; Jennings, P.E.; Brown, J.; Belch, J.J. Gliclazide: a general free radical scavenger. Eur. J. Pharmacol.,  1991, 208(2), 175-177.
[http://dx.doi.org/10.1016/0922-4106(91)90069-T] [PMID: 1800127 ] 
[134] 
Noda, Y.; Mori, A.; Packer, L. Gliclazide scavenges hydroxyl, superoxide and nitric oxide radicals: an ESR study. Res. Commun. Mol. Pathol. Pharmacol.,  1997, 96(2), 115-124.
[PMID: 9226746 ] 
[135] 
Corgnali, M.; Piconi, L.; Ihnat, M.; Ceriello, A. Evaluation of gliclazide ability to attenuate the hyperglycaemic ‘memory’ induced by high glucose in isolated human endothelial cells. Diabetes Metab. Res. Rev.,  2008, 24(4), 301-309.
[http://dx.doi.org/10.1002/dmrr.804] [PMID:  18088078] 
[136] 
Eriksson, L.; Nyström, T. Antidiabetic agents and endothelial dysfunction - beyond glucose control. Basic Clin. Pharmacol. Toxicol.,  2015, 117(1), 15-25.
[http://dx.doi.org/10.1111/bcpt.12402] [PMID:  25827165] 
[137] 
Tsuchiya, K.; Akaza, I.; Yoshimoto, T.; Hirata, Y. Pioglitazone improves endothelial function with increased adiponectin and high-density lipoprotein cholesterol levels in type 2 diabetes. Endocr. J.,  2009, 56(5), 691-698.
[http://dx.doi.org/10.1507/endocrj.K08E-308] [PMID:  19506330] 
[138] 
Kampoli, A.M.; Tousoulis, D.; Pallantza, Z.; Paterakis, G.; Papageorgiou, N.; Oikonomou, E.; Miliou, A.; Vlachopoulou, A.; Stefanadis, C. Comparable effects of pioglitazone and perindopril on circulating endothelial progenitor cells, inflammatory process and oxidative stress in patients with diabetes mellitus. Int. J. Cardiol.,  2012, 157(3), 413-415.
[http://dx.doi.org/10.1016/j.ijcard.2012.03.159] [PMID: 22494865 ] 
[139] 
Fernandez, M.; Triplitt, C.; Wajcberg, E.; Sriwijilkamol, A.A.; Musi, N.; Cusi, K.; DeFronzo, R.; Cersosimo, E. Addition of pioglitazone and ramipril to intensive insulin therapy in type 2 diabetic patients improves vascular dysfunction by different mechanisms. Diabetes Care,  2008, 31(1), 121-127.
[http://dx.doi.org/10.2337/dc07-0711] [PMID:  17909084 ] 
[140] 
Maegawa, H.; Nishio, Y.; Nakao, K.; Ugi, S.; Maeda, K.; Uzu, T.; Kashiwagi, A. Short-term low-dosage pioglitazone treatment improves vascular dysfunction in patients with type 2 diabetes. Endocr. J.,  2007, 54(4), 613-618.
[http://dx.doi.org/10.1507/endocrj.K06-203] [PMID: 17641441 ] 
[141] 
Kelly, A.S.; Thelen, A.M.; Kaiser, D.R.; Gonzalez-Campoy, J.M.; Bank, A.J. Rosiglitazone improves endothelial function and inflammation but not asymmetric dimethylarginine or oxidative stress in patients with type 2 diabetes mellitus. Vasc. Med.,  2007, 12(4), 311-318.
[http://dx.doi.org/10.1177/1358863X07084200] [PMID: 18048467 ] 
[142] 
Stojanović, M.; Prostran, M.; Radenković, M. Thiazolidinediones improve flow-mediated dilation: a meta-analysis of randomized clinical trials. Eur. J. Clin. Pharmacol.,  2016, 72(4), 385-398.
[http://dx.doi.org/10.1007/s00228-015-1999-4] [PMID: 26690770 ] 
[143] 
Radenković, M. Pioglitazone and endothelial dysfunction: pleiotropic effects and possible therapeutic implications. Sci. Pharm.,  2014, 82(4), 709-721.
[http://dx.doi.org/10.3797/scipharm.1407-16] [PMID:  26171320 ] 
[144] 
Boyle, J.G.; Logan, P.J.; Ewart, M.A.; Reihill, J.A.; Ritchie, S.A.; Connell, J.M.; Cleland, S.J.; Salt, I.P. Rosiglitazone stimulates nitric oxide synthesis in human aortic endothelial cells via AMP-activated protein kinase. J. Biol. Chem.,  2008, 283(17), 11210-11217.
[http://dx.doi.org/10.1074/jbc.M710048200] [PMID: 18303014 ] 
[145] 
Chen, C.; Peng, S.; Chen, F.; Liu, L.; Li, Z.; Zeng, G.; Huang, Q. Protective effects of pioglitazone on vascular endothelial cell dysfunction induced by high glucose via inhibition of IKKα/β-NFκB signaling mediated by PPARγ in vitro. Can. J. Physiol. Pharmacol.,  2017, 95(12), 1480-1487.
[http://dx.doi.org/10.1139/cjpp-2016-0574] [PMID: 28787583 ] 
[146] 
Werner, C.; Gensch, C.; Pöss, J.; Haendeler, J.; Böhm, M.; Laufs, U. Pioglitazone activates aortic telomerase and prevents stress-induced endothelial apoptosis. Atherosclerosis,  2011, 216(1), 23-34.
[http://dx.doi.org/10.1016/j.atherosclerosis.2011.02.011] [PMID: 21396644  ] 
[147] 
van Poppel, P.C.; Netea, M.G.; Smits, P.; Tack, C.J. Vildagliptin improves endothelium-dependent vasodilatation in type 2 diabetes. Diabetes Care,  2011, 34(9), 2072-2077.
[http://dx.doi.org/10.2337/dc10-2421] [PMID: 21788633 ] 
[148] 
Dell’Oro, R.; Maloberti, A.; Nicoli, F.; Villa, P.; Gamba, P.; Bombelli, M.; Mancia, G.; Grassi, G. Long-term saxagliptin treatment improves endothelial function but not pulse wave velocity and intima-media thickness in type 2 diabetic patients. High Blood Press. Cardiovasc. Prev.,  2017, 24(4), 393-400.
[http://dx.doi.org/10.1007/s40292-017-0215-2] [PMID: 28608024 ] 
[149] 
Dore, F.J.; Domingues, C.C.; Ahmadi, N.; Kundu, N.; Kropotova, Y.; Houston, S.; Rouphael, C.; Mammadova, A.; Witkin, L.; Khiyami, A.; Amdur, R.L.; Sen, S. The synergistic effects of saxagliptin and metformin on CD34+ endothelial progenitor cells in early type 2 diabetes patients: a randomized clinical trial. Cardiovasc. Diabetol.,  2018, 17(1), 65.
[http://dx.doi.org/10.1186/s12933-018-0709-9] [PMID: 29724198 ] 
[150] 
Nakamura, K.; Oe, H.; Kihara, H.; Shimada, K.; Fukuda, S.; Watanabe, K.; Takagi, T.; Yunoki, K.; Miyoshi, T.; Hirata, K.; Yoshikawa, J.; Ito, H. DPP-4 inhibitor and alpha-glucosidase inhibitor equally improve endothelial function in patients with type 2 diabetes: EDGE study. Cardiovasc. Diabetol.,  2014, 13, 110.
[http://dx.doi.org/10.1186/s12933-014-0110-2] [PMID: 25074318 ] 
[151] 
Kubota, Y.; Miyamoto, M.; Takagi, G.; Ikeda, T.; Kirinoki-Ichikawa, S.; Tanaka, K.; Mizuno, K. The dipeptidyl peptidase-4 inhibitor sitagliptin improves vascular endothelial function in type 2 diabetes. J. Korean Med. Sci.,  2012, 27(11), 1364-1370.
[http://dx.doi.org/10.3346/jkms.2012.27.11.1364] [PMID: 23166419  ] 
[152] 
Matsubara, J.; Sugiyama, S.; Sugamura, K.; Nakamura, T.; Fujiwara, Y.; Akiyama, E.; Kurokawa, H.; Nozaki, T.; Ohba, K.; Konishi, M.; Maeda, H.; Izumiya, Y.; Kaikita, K.; Sumida, H.; Jinnouchi, H.; Matsui, K.; Kim-Mitsuyama, S.; Takeya, M.; Ogawa, H. A dipeptidyl peptidase-4 inhibitor, des-fluoro-sitagliptin, improves endothelial function and reduces atherosclerotic lesion formation in apolipoprotein E-deficient mice. J. Am. Coll. Cardiol.,  2012, 59(3), 265-276.
[http://dx.doi.org/10.1016/j.jacc.2011.07.053] [PMID: 22240132 ] 
[153] 
Tremblay, A.J.; Lamarche, B.; Deacon, C.F.; Weisnagel, S.J.; Couture, P. Effects of sitagliptin therapy on markers of low-grade inflammation and cell adhesion molecules in patients with type 2 diabetes. Metabolism,  2014, 63(9), 1141-1148.
[http://dx.doi.org/10.1016/j.metabol.2014.06.004] [PMID: 25034387  ] 
[154] 
Fadini, G.P.; Boscaro, E.; Albiero, M.; Menegazzo, L.; Frison, V.; de Kreutzenberg, S.; Agostini, C.; Tiengo, A.; Avogaro, A. The oral dipeptidyl peptidase-4 inhibitor sitagliptin increases circulating endothelial progenitor cells in patients with type 2 diabetes: possible role of stromal-derived factor-1alpha. Diabetes Care,  2010, 33(7), 1607-1609.
[http://dx.doi.org/10.2337/dc10-0187] [PMID: 20357375 ] 
[155] 
Widlansky, M.E.; Puppala, V.K.; Suboc, T.M.; Malik, M.; Branum, A.; Signorelli, K.; Wang, J.; Ying, R.; Tanner, M.J.; Tyagi, S. Impact of DPP-4 inhibition on acute and chronic endothelial function in humans with type 2 diabetes on background metformin therapy. Vasc. Med.,  2017, 22(3), 189-196.
[http://dx.doi.org/10.1177/1358863X16681486] [PMID: 28145158 ] 
[156] 
Maruhashi, T.; Higashi, Y.; Kihara, Y.; Yamada, H.; Sata, M.; Ueda, S.; Odawara, M.; Terauchi, Y.; Dai, K.; Ohno, J.; Iida, M.; Sano, H.; Tomiyama, H.; Inoue, T.; Tanaka, A.; Murohara, T.; Node, K.; Investigators, P.S. PROLOGUE Study Investigators. Long-term effect of sitagliptin on endothelial function in type 2 diabetes: a sub-analysis of the PROLOGUE study. Cardiovasc. Diabetol.,  2016, 15(1), 134.
[http://dx.doi.org/10.1186/s12933-016-0438-x] [PMID: 27624168 ] 
[157] 
Nakamura, T.; Iwanaga, Y.; Miyaji, Y.; Nohara, R.; Ishimura, T.; Miyazaki, S. Sitagliptin Registry Kinki Cardiologists’ Study (SIRKAS) Investigators. Cardiovascular efficacy of sitagliptin in patients with diabetes at high risk of cardiovascular disease: a 12-month follow-up. Cardiovasc. Diabetol.,  2016, 15, 54.
[http://dx.doi.org/10.1186/s12933-016-0371-z] [PMID: 27036865 ] 
[158] 
Hage, C.; Brismar, K.; Lundman, P.; Norhammar, A.; Rydén, L.; Mellbin, L. The DPP-4 inhibitor sitagliptin and endothelial function in patients with acute coronary syndromes and newly detected glucose perturbations: A report from the BEGAMI study. Diab. Vasc. Dis. Res.,  2014, 11(4), 290-293.
[http://dx.doi.org/10.1177/1479164114533355] [PMID:  24845072 ] 
[159] 
Ayaori, M.; Iwakami, N.; Uto-Kondo, H.; Sato, H.; Sasaki, M.; Komatsu, T.; Iizuka, M.; Takiguchi, S.; Yakushiji, E.; Nakaya, K.; Yogo, M.; Ogura, M.; Takase, B.; Murakami, T.; Ikewaki, K. Dipeptidyl peptidase-4 inhibitors attenuate endothelial function as evaluated by flow-mediated vasodilatation in type 2 diabetic patients. J. Am. Heart Assoc.,  2013, 2(1)e003277
[http://dx.doi.org/10.1161/JAHA.112.003277] [PMID: 23525426 ] 
[160] 
Tripolt, N.J.; Aberer, F.; Riedl, R.; Url, J.; Dimsity, G.; Meinitzer, A.; Stojakovic, T.; Aziz, F.; Hödl, R.; Brachtl, G.; Strunk, D.; Brodmann, M.; Hafner, F.; Sourij, H. Effects of linagliptin on endothelial function and postprandial lipids in coronary artery disease patients with early diabetes: a randomized, placebo-controlled, double-blind trial. Cardiovasc. Diabetol.,  2018, 17(1), 71.
[http://dx.doi.org/10.1186/s12933-018-0716-x] [PMID: 29773079 ] 
[161] 
Baltzis, D.; Dushay, J.R.; Loader, J.; Wu, J.; Greenman, R.L.; Roustit, M.; Veves, A. Effect of linagliptin on vascular function: a randomized, placebo-controlled study. J. Clin. Endocrinol. Metab.,  2016, 101(11), 4205-4213.
[http://dx.doi.org/10.1210/jc.2016-2655] [PMID: 27583476 ] 
[162] 
Zhong, J.; Maiseyeu, A.; Davis, S.N.; Rajagopalan, S. DPP4 in cardiometabolic disease: recent insights from the laboratory and clinical trials of DPP4 inhibition. Circ. Res.,  2015, 116(8), 1491-1504.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.305665] [PMID: 25858071 ] 
[163] 
Ishii, M.; Shibata, R.; Kondo, K.; Kambara, T.; Shimizu, Y.; Tanigawa, T.; Bando, Y.K.; Nishimura, M.; Ouchi, N.; Murohara, T. Vildagliptin stimulates endothelial cell network formation and ischemia-induced revascularization via an endothelial nitric-oxide synthase-dependent mechanism. J. Biol. Chem.,  2014, 289(39), 27235-27245.
[http://dx.doi.org/10.1074/jbc.M114.557835] [PMID: 25100725 ] 
[164] 
Shah, Z.; Pineda, C.; Kampfrath, T.; Maiseyeu, A.; Ying, Z.; Racoma, I.; Deiuliis, J.; Xu, X.; Sun, Q.; Moffatt-Bruce, S.; Villamena, F.; Rajagopalan, S. Acute DPP-4 inhibition modulates vascular tone through GLP-1 independent pathways. Vascul. Pharmacol.,  2011, 55(1-3), 2-9.
[http://dx.doi.org/10.1016/j.vph.2011.03.001] [PMID: 21397040 ] 
[165] 
Forst, T.; Michelson, G.; Ratter, F.; Weber, M.M.; Anders, S.; Mitry, M.; Wilhelm, B.; Pfützner, A. Addition of liraglutide in patients with Type 2 diabetes well controlled on metformin monotherapy improves several markers of vascular function. Diabet. Med.,  2012, 29(9), 1115-1118.
[http://dx.doi.org/10.1111/j.1464-5491.2012.03589.x] [PMID: 22288732 ] 
[166] 
Faber, R.; Zander, M.; Pena, A.; Michelsen, M.M.; Mygind, N.D.; Prescott, E. Effect of the glucagon-like peptide-1 analogue liraglutide on coronary microvascular function in patients with type 2 diabetes - a randomized, single-blinded, cross-over pilot study. Cardiovasc. Diabetol.,  2015, 14, 41.
[http://dx.doi.org/10.1186/s12933-015-0206-3] [PMID: 25896352 ] 
[167] 
Nomoto, H.; Miyoshi, H.; Furumoto, T.; Oba, K.; Tsutsui, H.; Miyoshi, A.; Kondo, T.; Tsuchida, K.; Atsumi, T.; Manda, N.; Kurihara, Y.; Aoki, S.; Group, S.S. SAIS Study Group. A comparison of the effects of the GLP-1 analogue liraglutide and insulin glargine on endothelial function and metabolic parameters: a randomized, controlled trial sapporo athero-incretin study 2 (SAIS2). PLoS One,  2015, 10(8)e0135854
[http://dx.doi.org/10.1371/journal.pone.0135854] [PMID: 26284918 ] 
[168] 
Hopkins, N.D.; Cuthbertson, D.J.; Kemp, G.J.; Pugh, C.; Green, D.J.; Cable, N.T.; Jones, H. Effects of 6 months glucagon-like peptide-1 receptor agonist treatment on endothelial function in type 2 diabetes mellitus patients. Diabetes Obes. Metab.,  2013, 15(8), 770-773.
[http://dx.doi.org/10.1111/dom.12089] [PMID: 23451821 ] 
[169] 
Gurkan, E.; Tarkun, I.; Sahin, T.; Cetinarslan, B.; Canturk, Z. Evaluation of exenatide versus insulin glargine for the impact on endothelial functions and cardiovascular risk markers. Diabetes Res. Clin. Pract.,  2014, 106(3), 567-575.
[http://dx.doi.org/10.1016/j.diabres.2014.09.046] [PMID: 25458329 ] 
[170] 
Hu, Y.; Liu, J.; Wang, G.; Xu, Y. The effects of exenatide and metformin on endothelial function in newly diagnosed type 2 diabetes mellitus patients: a case-control study. Diabetes Ther.,  2018, 9(3), 1295-1305.
[http://dx.doi.org/10.1007/s13300-018-0435-z] [PMID: 29754323 ] 
[171] 
Ceriello, A.; Novials, A.; Ortega, E.; Canivell, S.; La Sala, L.; Pujadas, G.; Esposito, K.; Giugliano, D.; Genovese, S. Glucagon-like peptide 1 reduces endothelial dysfunction, inflammation, and oxidative stress induced by both hyperglycemia and hypoglycemia in type 1 diabetes. Diabetes Care,  2013, 36(8), 2346-2350.
[http://dx.doi.org/10.2337/dc12-2469] [PMID: 23564922 ] 
[172] 
Kelly, A.S.; Bergenstal, R.M.; Gonzalez-Campoy, J.M.; Katz, H.; Bank, A.J. Effects of exenatide vs. metformin on endothelial function in obese patients with pre-diabetes: a randomized trial. Cardiovasc. Diabetol.,  2012, 11, 64.
[http://dx.doi.org/10.1186/1475-2840-11-64] [PMID: 22681705 ] 
[173] 
Liu, H.; Hu, Y.; Simpson, R.W.; Dear, A.E. Glucagon-like peptide-1 attenuates tumour necrosis factor-alpha-mediated induction of plasminogen [corrected] activator inhibitor-1 expression. J. Endocrinol.,  2008, 196(1), 57-65.
[http://dx.doi.org/10.1677/JOE-07-0387] [PMID: 18180317 ] 
[174] 
Ishibashi, Y.; Matsui, T.; Takeuchi, M.; Yamagishi, S. Glucagon-like peptide-1 (GLP-1) inhibits advanced glycation end product (AGE)-induced up-regulation of VCAM-1 mRNA levels in endothelial cells by suppressing AGE receptor (RAGE) expression. Biochem. Biophys. Res. Commun.,  2010, 391(3), 1405-1408.
[http://dx.doi.org/10.1016/j.bbrc.2009.12.075] [PMID:  20026306 ] 
[175] 
Ding, L.; Zhang, J. Glucagon-like peptide-1 activates endothelial nitric oxide synthase in human umbilical vein endothelial cells. Acta Pharmacol. Sin.,  2012, 33(1), 75-81.
[http://dx.doi.org/10.1038/aps.2011.149] [PMID: 22120969 ] 
[176] 
Xiao-Yun, X.; Zhao-Hui, M.; Ke, C.; Hong-Hui, H.; Yan-Hong, X. Glucagon-like peptide-1 improves proliferation and differentiation of endothelial progenitor cells via upregulating VEGF generation. Med. Sci. Monit.,  2011, 17(2), BR35-BR41.
[http://dx.doi.org/10.12659/MSM.881383] [PMID: 21278683 ] 
[177] 
Schisano, B.; Harte, A.L.; Lois, K.; Saravanan, P.; Al-Daghri, N.; Al-Attas, O.; Knudsen, L.B.; McTernan, P.G.; Ceriello, A.; Tripathi, G. GLP-1 analogue, Liraglutide protects human umbilical vein endothelial cells against high glucose induced endoplasmic reticulum stress. Regul. Pept.,  2012, 174(1-3), 46-52.
[http://dx.doi.org/10.1016/j.regpep.2011.11.008] [PMID: 22120833 ] 
[178] 
Gaspari, T.; Liu, H.; Welungoda, I.; Hu, Y.; Widdop, R.E.; Knudsen, L.B.; Simpson, R.W.; Dear, A.E.A.A. GLP-1 receptor agonist liraglutide inhibits endothelial cell dysfunction and vascular adhesion molecule expression in an ApoE-/- mouse model. Diab. Vasc. Dis. Res.,  2011, 8(2), 117-124.
[http://dx.doi.org/10.1177/1479164111404257] [PMID: 21562063 ] 
[179] 
Tanaka, A.; Shimabukuro, M.; Okada, Y.; Taguchi, I.; Yamaoka-Tojo, M.; Tomiyama, H.; Teragawa, H.; Sugiyama, S.; Yoshida, H.; Sato, Y.; Kawaguchi, A.; Ikehara, Y.; Machii, N.; Maruhashi, T.; Shima, K.R.; Takamura, T.; Matsuzawa, Y.; Kimura, K.; Sakuma, M.; Oyama, J.I.; Inoue, T.; Higashi, Y.; Ueda, S.; Node, K.; Investigators, E.T. EMBLEM Trial Investigators. Rationale and design of a multicenter placebo-controlled double-blind randomized trial to evaluate the effect of empagliflozin on endothelial function: the EMBLEM trial. Cardiovasc. Diabetol.,  2017, 16(1), 48.
[http://dx.doi.org/10.1186/s12933-017-0532-8] [PMID: 28403850 ] 
[180] 
Solini, A.; Giannini, L.; Seghieri, M.; Vitolo, E.; Taddei, S.; Ghiadoni, L.; Bruno, R.M. Dapagliflozin acutely improves endothelial dysfunction, reduces aortic stiffness and renal resistive index in type 2 diabetic patients: a pilot study. Cardiovasc. Diabetol.,  2017, 16(1), 138.
[http://dx.doi.org/10.1186/s12933-017-0621-8] [PMID: 29061124 ] 
[181] 
Sugiyama, S.; Jinnouchi, H.; Kurinami, N.; Hieshima, K.; Yoshida, A.; Jinnouchi, K.; Nishimura, H.; Suzuki, T.; Miyamoto, F.; Kajiwara, K.; Jinnouchi, T. The SGLT2 inhibitor dapagliflozin significantly improves the peripheral microvascular endothelial function in patients with uncontrolled type 2 diabetes mellitus. Intern. Med.,  2018, 57(15), 2147-2156.
[http://dx.doi.org/10.2169/internalmedicine.0701-17] [PMID: 29607968 ] 
[182] 
Gaspari, T.; Spizzo, I.; Liu, H.; Hu, Y.; Simpson, R.W.; Widdop, R.E.; Dear, A.E. Dapagliflozin attenuates human vascular endothelial cell activation and induces vasorelaxation: A potential mechanism for inhibition of atherogenesis. Diab. Vasc. Dis. Res.,  2018, 15(1), 64-73.
[http://dx.doi.org/10.1177/1479164117733626] [PMID: 28976221 ] 
[183] 
Lee, D.M.; Battson, M.L.; Jarrell, D.K.; Hou, S.; Ecton, K.E.; Weir, T.L.; Gentile, C.L. SGLT2 inhibition via dapagliflozin improves generalized vascular dysfunction and alters the gut microbiota in type 2 diabetic mice. Cardiovasc. Diabetol.,  2018, 17(1), 62.
[http://dx.doi.org/10.1186/s12933-018-0708-x] [PMID: 29703207 ] 
[184] 
Li, H.; Shin, S.E.; Seo, M.S.; An, J.R.; Choi, I.W.; Jung, W.K.; Firth, A.L.; Lee, D.S.; Yim, M.J.; Choi, G.; Lee, J.M.; Na, S.H.; Park, W.S. The anti-diabetic drug dapagliflozin induces vasodilation via activation of PKG and Kv channels. Life Sci.,  2018, 197, 46-55.
[http://dx.doi.org/10.1016/j.lfs.2018.01.032] [PMID: 29409796 ] 
[185] 
Oelze, M.; Kröller-Schön, S.; Welschof, P.; Jansen, T.; Hausding, M.; Mikhed, Y.; Stamm, P.; Mader, M.; Zinßius, E.; Agdauletova, S.; Gottschlich, A.; Steven, S.; Schulz, E.; Bottari, S.P.; Mayoux, E.; Münzel, T.; Daiber, A. The sodium-glucose co-transporter 2 inhibitor empagliflozin improves diabetes-induced vascular dysfunction in the streptozotocin diabetes rat model by interfering with oxidative stress and glucotoxicity. PLoS One,  2014, 9(11)e112394
[http://dx.doi.org/10.1371/journal.pone.0112394] [PMID: 25402275 ] 
[186] 
Lin, B.; Koibuchi, N.; Hasegawa, Y.; Sueta, D.; Toyama, K.; Uekawa, K.; Ma, M.; Nakagawa, T.; Kusaka, H.; Kim-Mitsuyama, S. Glycemic control with empagliflozin, a novel selective SGLT2 inhibitor, ameliorates cardiovascular injury and cognitive dysfunction in obese and type 2 diabetic mice. Cardiovasc. Diabetol.,  2014, 13, 148.
[http://dx.doi.org/10.1186/s12933-014-0148-1] [PMID: 25344694 ] 
[187] 
Tahara, A.; Takasu, T.; Yokono, M.; Imamura, M.; Kurosaki, E. Characterization and comparison of SGLT2 inhibitors: Part 3. Effects on diabetic complications in type 2 diabetic mice. Eur. J. Pharmacol.,  2017, 809, 163-171.
[http://dx.doi.org/10.1016/j.ejphar.2017.05.019] [PMID: 28506912 ] 
[188] 
Marso, S.P.; McGuire, D.K.; Zinman, B.; Poulter, N.R.; Emerson, S.S.; Pieber, T.R.; Pratley, R.E.; Haahr, P.M.; Lange, M.; Brown-Frandsen, K.; Moses, A.; Skibsted, S.; Kvist, K.; Buse, J.B.; Group, D.S. DEVOTE study group. efficacy and safety of degludec versus glargine in type 2 diabetes. N. Engl. J. Med.,  2017, 377(8), 723-732.
[http://dx.doi.org/10.1056/NEJMoa1615692] [PMID: 28605603 ] 
[189] 
Gerstein, H.C.; Bosch, J.; Dagenais, G.R.; Díaz, R.; Jung, H.; Maggioni, A.P.; Pogue, J.; Probstfield, J.; Ramachandran, A.; Riddle, M.C.; Rydén, L.E.; Yusuf, S. ORIGIN Trial Investigators. Basal insulin and cardiovascular and other outcomes in dysglycemia. N. Engl. J. Med.,  2012, 367(4), 319-328.
[http://dx.doi.org/10.1056/NEJMoa1203858] [PMID: 22686416 ] 
[190] 
Madenidou, A.V.; Paschos, P.; Karagiannis, T.; Katsoula, A.; Athanasiadou, E.; Kitsios, K.; Bekiari, E.; Matthews, D.R.; Tsapas, A. Comparative benefits and harms of basal insulin analogues for type 2 diabetes: a systematic review and network meta-analysis. Ann. Intern. Med.,  2018, 169(3), 165-174.
[http://dx.doi.org/10.7326/M18-0443] [PMID: 29987326 ] 
[191] 
Tentolouris, A.; Eleftheriadou, I.; Tentolouris, N. Insulin degludec U100 is associated with lower risk for severe and symptomatic hypoglycemia as compared with insulin glargine U100 in subjects with type 1 diabetes. Ann. Transl. Med.,  2018, 6(3), 63.
[http://dx.doi.org/10.21037/atm.2017.12.28] [PMID: 29610753 ] 
[192] 
Oikonomou, D.; Kopf, S.; von Bauer, R.; Djuric, Z.; Cebola, R.; Sander, A.; Englert, S.; Vittas, S.; Hidmark, A.; Morcos, M.; Korosoglou, G.; Nawroth, P.P.; Humpert, P.M. Influence of insulin and glargine on outgrowth and number of circulating endothelial progenitor cells in type 2 diabetes patients: a partially double-blind, randomized, three-arm unicenter study. Cardiovasc. Diabetol.,  2014, 13, 137.
[http://dx.doi.org/10.1186/s12933-014-0137-4] [PMID: 25300286 ] 
[193] 
Baigent, C.; Blackwell, L.; Emberson, J.; Holland, L.E.; Reith, C.; Bhala, N.; Peto, R.; Barnes, E.H.; Keech, A.; Simes, J.; Collins, R. Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet,  2010, 376(9753), 1670-1681.
[http://dx.doi.org/10.1016/S0140-6736(10)61350-5] [PMID: 21067804 ] 
[194] 
American Diabetes Association. 9. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes-2018. Diabetes Care,  2018, 41(Suppl. 1), S86-S104.
[http://dx.doi.org/10.2337/dc18-S009] [PMID: 29222380 ] 
[195] 
Oesterle, A.; Laufs, U.; Liao, J.K. Pleiotropic effects of statins on the cardiovascular system. Circ. Res.,  2017, 120(1), 229-243.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.308537] [PMID: 28057795 ] 
[196] 
Grigoropoulou, P.; Tentolouris, A.; Eleftheriadou, I.; Tsilingiris, D.; Vlachopoulos, C.; Sykara, M.; Tentolouris, N. Effect of 12-month intervention with low-dose atorvastatin on pulse wave velocity in subjects with type 2 diabetes and dyslipidaemia. Diab. Vasc. Dis. Res.,  2019, 16(1), 38-46.
[http://dx.doi.org/10.1177/1479164118805320] [PMID: 30328360 ] 
[197] 
Laufs, U.; La Fata, V.; Plutzky, J.; Liao, J.K. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation,  1998, 97(12), 1129-1135.
[http://dx.doi.org/10.1161/01.CIR.97.12.1129] [PMID:  9537338 ] 
[198] 
Laufs, U.; Liao, J.K. Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. J. Biol. Chem.,  1998, 273(37), 24266-24271.
[http://dx.doi.org/10.1074/jbc.273.37.24266] [PMID: 9727051 ] 
[199] 
Takemoto, M.; Sun, J.; Hiroki, J.; Shimokawa, H.; Liao, J.K. Rho-kinase mediates hypoxia-induced downregulation of endothelial nitric oxide synthase. Circulation,  2002, 106(1), 57-62.
[http://dx.doi.org/10.1161/01.CIR.0000020682.73694.AB] [PMID: 12093770 ] 
[200] 
Dimmeler, S.; Fleming, I.; Fisslthaler, B.; Hermann, C.; Busse, R.; Zeiher, A.M. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature,  1999, 399(6736), 601-605.
[http://dx.doi.org/10.1038/21224] [PMID: 10376603 ] 
[201] 
Wolfrum, S.; Dendorfer, A.; Rikitake, Y.; Stalker, T.J.; Gong, Y.; Scalia, R.; Dominiak, P.; Liao, J.K. Inhibition of Rho-kinase leads to rapid activation of phosphatidylinositol 3-kinase/protein kinase Akt and cardiovascular protection. Arterioscler. Thromb. Vasc. Biol.,  2004, 24(10), 1842-1847.
[http://dx.doi.org/10.1161/01.ATV.0000142813.33538.82] [PMID: 15319269 ] 
[202] 
Pelat, M.; Dessy, C.; Massion, P.; Desager, J.P.; Feron, O.; Balligand, J.L. Rosuvastatin decreases caveolin-1 and improves nitric oxide-dependent heart rate and blood pressure variability in apolipoprotein E-/- mice in vivo. Circulation,  2003, 107(19), 2480-2486.
[http://dx.doi.org/10.1161/01.CIR.0000065601.83526.3E] [PMID: 12719275 ] 
[203] 
Wassmann, S.; Laufs, U.; Müller, K.; Konkol, C.; Ahlbory, K.; Bäumer, A.T.; Linz, W.; Böhm, M.; Nickenig, G. Cellular antioxidant effects of atorvastatin in vitro and in vivo. Arterioscler. Thromb. Vasc. Biol.,  2002, 22(2), 300-305.
[http://dx.doi.org/10.1161/hq0202.104081] [PMID: 11834532 ] 
[204] 
Zhang, L.; Gong, D.; Li, S.; Zhou, X. Meta-analysis of the effects of statin therapy on endothelial function in patients with diabetes mellitus. Atherosclerosis,  2012, 223(1), 78-85.
[http://dx.doi.org/10.1016/j.atherosclerosis.2012.01.031] [PMID: 22326029 ] 
[205] 
Murrow, J.R.; Sher, S.; Ali, S.; Uphoff, I.; Patel, R.; Porkert, M.; Le, N.A.; Jones, D.; Quyyumi, A.A. The differential effect of statins on oxidative stress and endothelial function: atorvastatin versus pravastatin. J. Clin. Lipidol.,  2012, 6(1), 42-49.
[http://dx.doi.org/10.1016/j.jacl.2011.08.006] [PMID: 22264573 ] 
[206] 
Kim, K.M.; Jung, K.Y.; Yun, H.M.; Lee, S.Y.; Oh, T.J.; Jang, H.C.; Lim, S. Effect of rosuvastatin on fasting and postprandial endothelial biomarker levels and microvascular reactivity in patients with type 2 diabetes and dyslipidemia: a preliminary report. Cardiovasc. Diabetol.,  2017, 16(1), 146.
[http://dx.doi.org/10.1186/s12933-017-0629-0] [PMID: 29121934 ] 
[207] 
Katsiki, N.; Reiner, Ž.; Tedeschi Reiner, E.; Al-Rasadi, K.; Pirro, M.; Mikhailidis, D.P.; Sahebkar, A. Improvement of endothelial function by pitavastatin: a meta-analysis. Expert Opin. Pharmacother.,  2018, 19(3), 279-286.
[http://dx.doi.org/10.1080/14656566.2018.1428560] [PMID: 29334477  ] 
[208] 
Vasa, M.; Fichtlscherer, S.; Adler, K.; Aicher, A.; Martin, H.; Zeiher, A.M.; Dimmeler, S. Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation,  2001, 103(24), 2885-2890.
[http://dx.doi.org/10.1161/hc2401.092816] [PMID: 11413075 ] 
[209] 
Oikonomou, E.; Siasos, G.; Zaromitidou, M.; Hatzis, G.; Mourouzis, K.; Chrysohoou, C.; Zisimos, K.; Mazaris, S.; Tourikis, P.; Athanasiou, D.; Stefanadis, C.; Papavassiliou, A.G.; Tousoulis, D. Atorvastatin treatment improves endothelial function through endothelial progenitor cells mobilization in ischemic heart failure patients. Atherosclerosis,  2015, 238(2), 159-164.
[http://dx.doi.org/10.1016/j.atherosclerosis.2014.12.014] [PMID: 25525743 ] 
[210] 
Goya, K.; Sumitani, S.; Xu, X.; Kitamura, T.; Yamamoto, H.; Kurebayashi, S.; Saito, H.; Kouhara, H.; Kasayama, S.; Kawase, I. Peroxisome proliferator-activated receptor alpha agonists increase nitric oxide synthase expression in vascular endothelial cells. Arterioscler. Thromb. Vasc. Biol.,  2004, 24(4), 658-663.
[http://dx.doi.org/10.1161/01.ATV.0000118682.58708.78] [PMID: 14751809 ] 
[211] 
Liu, J.; Lu, C.; Li, F.; Wang, H.; He, L.; Hao, Y.; Chen, A.F.; An, H.; Wang, X.; Hong, T.; Wang, G. PPAR-α agonist fenofibrate upregulates tetrahydrobiopterin level through increasing the expression of guanosine 5′-triphosphate cyclohydrolase-i in human umbilical vein endothelial cells. PPAR Res.,  2011, 2011523520
[http://dx.doi.org/10.1155/2011/523520] [PMID: 22190909 ] 
[212] 
Irukayama-Tomobe, Y.; Miyauchi, T.; Kasuya, Y.; Sakai, S.; Goto, K.; Yamaguchi, I. Activation of peroxisome proliferator-activated receptor-alpha decreases endothelin-1-induced p38 mitogen-activated protein kinase activation in cardiomyocytes. J. Cardiovasc. Pharmacol.,  2004, 44(Suppl. 1), S358-S361.
[http://dx.doi.org/10.1097/01.fjc.0000166303.33313.01] [PMID: 15838320 ] 
[213] 
Playford, D.A.; Watts, G.F.; Best, J.D.; Burke, V. Effect of fenofibrate on brachial artery flow-mediated dilatation in type 2 diabetes mellitus. Am. J. Cardiol.,  2002, 90(11), 1254-1257.
[http://dx.doi.org/10.1016/S0002-9149(02)02847-3] [PMID: 12450611 ] 
[214] 
Ghani, R.A.; Bin Yaakob, I.; Wahab, N.A.; Zainudin, S.; Mustafa, N.; Sukor, N.; Wan Mohamud, W.N.; Kadir, K.A.; Kamaruddin, N.A. The influence of fenofibrate on lipid profile, endothelial dysfunction, and inflammatory markers in type 2 diabetes mellitus patients with typical and mixed dyslipidemia. J. Clin. Lipidol.,  2013, 7(5), 446-453.
[http://dx.doi.org/10.1016/j.jacl.2013.04.004] [PMID: 24079286 ] 
[215] 
Sahebkar, A.; Giua, R.; Pedone, C.; Ray, K.K.; Vallejo-Vaz, A.J.; Costanzo, L. Fibrate therapy and flow-mediated dilation: A systematic review and meta-analysis of randomized placebo-controlled trials. Pharmacol. Res.,  2016, 111, 163-179.
[http://dx.doi.org/10.1016/j.phrs.2016.06.011] [PMID: 27320045 ] 
[216] 
Harmer, J.A.; Keech, A.C.; Veillard, A.S.; Skilton, M.R.; Marwick, T.H.; Watts, G.F.; Meredith, I.T.; Celermajer, D.S.; Investigators, F.V.S. FIELD Vascular Study Investigators. Fenofibrate effects on arterial endothelial function in adults with type 2 diabetes mellitus: A FIELD substudy. Atherosclerosis,  2015, 242(1), 295-302.
[http://dx.doi.org/10.1016/j.atherosclerosis.2015.07.038] [PMID: 26233916 ] 
[217] 
Blanco-Rivero, J.; Márquez-Rodas, I.; Xavier, F.E.; Aras-López, R.; Arroyo-Villa, I.; Ferrer, M.; Balfagón, G. Long-term fenofibrate treatment impairs endothelium-dependent dilation to acetylcholine by altering the cyclooxygenase pathway. Cardiovasc. Res.,  2007, 75(2), 398-407.
[http://dx.doi.org/10.1016/j.cardiores.2007.03.006] [PMID: 17412316  ] 
[218] 
Sugiyama, S.; Jinnouchi, H.; Hieshima, K.; Kurinami, N.; Suzuki, T.; Miyamoto, F.; Kajiwara, K.; Matsui, K.; Jinnouchi, T. A pilot study of ezetimibe vs. atorvastatin for improving peripheral microvascular endothelial function in stable patients with type 2 diabetes mellitus. Lipids Health Dis.,  2015, 14, 37.
[http://dx.doi.org/10.1186/s12944-015-0028-z] [PMID: 25903215 ] 
[219] 
Nochioka, K.; Tanaka, S.; Miura, M.; Zhulanqiqige, E.; Fukumoto, Y.; Shiba, N.; Shimokawa, H. Ezetimibe improves endothelial function and inhibits Rho-kinase activity associated with inhibition of cholesterol absorption in humans. Circ. J.,  2012, 76(8), 2023-2030.
[http://dx.doi.org/10.1253/circj.CJ-12-0331] [PMID: 22640986 ] 
[220] 
Shinnakasu, A.; Yamamoto, K.; Kurano, M.; Arimura, H.; Arimura, A.; Kikuti, A.; Hashiguchi, H.; Deguchi, T.; Nishio, Y. The combination therapy of fenofibrate and ezetimibe improved lipid profile and vascular function compared with statins in patients with type 2 diabetes. J. Atheroscler. Thromb.,  2017, 24(7), 735-748.
[http://dx.doi.org/10.5551/jat.39446] [PMID: 28450679 ] 
[221] 
Vane, J.R.; Botting, R.M. The mechanism of action of aspirin. Thromb. Res.,  2003, 110(5-6), 255-258.
[http://dx.doi.org/10.1016/S0049-3848(03)00379-7] [PMID: 14592543 ] 
[222] 
Dzeshka, M.S.; Shantsila, A.; Lip, G.Y. Effects of aspirin on endothelial function and hypertension. Curr. Hypertens. Rep.,  2016, 18(11), 83.
[http://dx.doi.org/10.1007/s11906-016-0688-8] [PMID: 27787837 ] 
[223] 
Schrottmaier, W.C.; Kral, J.B.; Badrnya, S.; Assinger, A. Aspirin and P2Y12 Inhibitors in platelet-mediated activation of neutrophils and monocytes. Thromb. Haemost.,  2015, 114(3), 478-489.
[http://dx.doi.org/10.1160/TH14-11-0943] [PMID: 25904241 ] 
[224] 
Thomas, M.R.; Storey, R.F. The role of platelets in inflammation. Thromb. Haemost.,  2015, 114(3), 449-458.
[PMID: 26293514 ] 
[225] 
Ellinsworth, D.C.; Shukla, N.; Fleming, I.; Jeremy, J.Y. Interactions between thromboxane A2, thromboxane/prostaglandin (TP) receptors, and endothelium-derived hyperpolarization. Cardiovasc. Res.,  2014, 102(1), 9-16.
[http://dx.doi.org/10.1093/cvr/cvu015] [PMID: 24469536 ] 
[226] 
Capra, V.; Bäck, M.; Angiolillo, D.J.; Cattaneo, M.; Sakariassen, K.S. Impact of vascular thromboxane prostanoid receptor activation on hemostasis, thrombosis, oxidative stress, and inflammation. J. Thromb. Haemost.,  2014, 12(2), 126-137.
[http://dx.doi.org/10.1111/jth.12472] [PMID: 24298905 ] 
[227] 
Heiss, E.H.; Dirsch, V.M. Regulation of eNOS enzyme activity by posttranslational modification. Curr. Pharm. Des.,  2014, 20(22), 3503-3513.
[http://dx.doi.org/10.2174/13816128113196660745] [PMID: 24180389 ] 
[228] 
Jung, S.B.; Kim, C.S.; Naqvi, A.; Yamamori, T.; Mattagajasingh, I.; Hoffman, T.A.; Cole, M.P.; Kumar, A.; Dericco, J.S.; Jeon, B.H.; Irani, K. Histone deacetylase 3 antagonizes aspirin-stimulated endothelial nitric oxide production by reversing aspirin-induced lysine acetylation of endothelial nitric oxide synthase. Circ. Res.,  2010, 107(7), 877-887.
[http://dx.doi.org/10.1161/CIRCRESAHA.110.222968] [PMID: 20705923 ] 
[229] 
Taubert, D.; Berkels, R.; Grosser, N.; Schröder, H.; Gründemann, D.; Schömig, E. Aspirin induces nitric oxide release from vascular endothelium: a novel mechanism of action. Br. J. Pharmacol.,  2004, 143(1), 159-165.
[http://dx.doi.org/10.1038/sj.bjp.0705907] [PMID: 15289285 ] 
[230] 
Schror, K.; Rauch, B. H. Aspirin and lipid mediators in the
cardiovascular system.Prostaglandins & other lipid mediators. Prostaglandins Other Lipid Mediat,  2015, 121(Pt A), 17-23.
[http://dx.doi.org/10.1016/j.prostaglandins.2015.07.004] [PMID: 26201059 ] 
[231] 
Romano, M.; Cianci, E.; Simiele, F.; Recchiuti, A. Lipoxins and aspirin-triggered lipoxins in resolution of inflammation. Eur. J. Pharmacol.,  2015, 760, 49-63.
[http://dx.doi.org/10.1016/j.ejphar.2015.03.083] [PMID: 25895638 ] 
[232] 
Ho, K.J.; Spite, M.; Owens, C.D.; Lancero, H.; Kroemer, A.H.; Pande, R.; Creager, M.A.; Serhan, C.N.; Conte, M.S. Aspirin-triggered lipoxin and resolvin E1 modulate vascular smooth muscle phenotype and correlate with peripheral atherosclerosis. Am. J. Pathol.,  2010, 177(4), 2116-2123.
[http://dx.doi.org/10.2353/ajpath.2010.091082] [PMID: 20709806 ] 
[233] 
Félétou, M.; Huang, Y.; Vanhoutte, P.M. Endothelium-mediated control of vascular tone: COX-1 and COX-2 products. Br. J. Pharmacol.,  2011, 164(3), 894-912.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01276.x] [PMID: 21323907 ] 
[234] 
Tassone, E.J.; Perticone, M.; Sciacqua, A.; Mafrici, S.F.; Settino, C.; Malara, N.; Mollace, V.; Sesti, G.; Perticone, F. Low dose of acetylsalicylic acid and oxidative stress-mediated endothelial dysfunction in diabetes: a short-term evaluation. Acta Diabetol.,  2015, 52(2), 249-256.
[http://dx.doi.org/10.1007/s00592-014-0629-4] [PMID: 25091345 ] 
[235] 
Magen, E.; Viskoper, J.R.; Mishal, J.; Priluk, R.; London, D.; Yosefy, C. Effects of low-dose aspirin on blood pressure and endothelial function of treated hypertensive hypercholesterolaemic subjects. J. Hum. Hypertens.,  2005, 19(9), 667-673.
[http://dx.doi.org/10.1038/sj.jhh.1001910] [PMID: 16034448 ] 
[236] 
Bulut, D.; Becker, V.; Mügge, A. Acetylsalicylate reduces endothelial and platelet-derived microparticles in patients with coronary artery disease. Can. J. Physiol. Pharmacol.,  2011, 89(4), 239-244.
[http://dx.doi.org/10.1139/y11-013] [PMID: 21539467 ] 
[237] 
Raghavan, R.P.; Laight, D.W.; Cummings, M.H. Aspirin in type 2 diabetes, a randomised controlled study: effect of different doses on inflammation, oxidative stress, insulin resistance and endothelial function. Int. J. Clin. Pract.,  2014, 68(2), 271-277.
[http://dx.doi.org/10.1111/ijcp.12310] [PMID: 24372992 ] 
[238] 
Cameron, S.J.; Goulopoulou, S.; Weil, B.R.; Kanaley, J.A. Regulation of blood flow by aspirin following muscle ischemia. Eur. Rev. Med. Pharmacol. Sci.,  2012, 16(2), 143-150.
[PMID: 22428464 ] 
[239] 
Campia, U.; Choucair, W.K.; Bryant, M.B.; Quyyumi, A.A.; Cardillo, C.; Panza, J.A. Role of cyclooxygenase products in the regulation of vascular tone and in the endothelial vasodilator function of normal, hypertensive, and hypercholesterolemic humans. Am. J. Cardiol.,  2002, 89(3), 286-290.
[http://dx.doi.org/10.1016/S0002-9149(01)02229-9] [PMID: 11809430 ] 
[240] 
Yamanari, H.; Nakamura, K.; Kakishita, M.; Ohe, T. Effects of cyclooxygenase inhibition on endothelial function in hypertensive patients treated with angiotensin-converting enzyme inhibitors. Clin. Cardiol.,  2004, 27(9), 523-527.
[http://dx.doi.org/10.1002/clc.4960270911] [PMID: 15471166 ] 
[241] 
Husain, S.; Andrews, N.P.; Mulcahy, D.; Panza, J.A.; Quyyumi, A.A. Aspirin improves endothelial dysfunction in atherosclerosis. Circulation,  1998, 97(8), 716-720.
[http://dx.doi.org/10.1161/01.CIR.97.8.716] [PMID: 9498533 ] 
[242] 
Noon, J.P.; Walker, B.R.; Hand, M.F.; Webb, D.J. Impairment of forearm vasodilatation to acetylcholine in hypercholesterolemia is reversed by aspirin. Cardiovasc. Res.,  1998, 38(2), 480-484.
[http://dx.doi.org/10.1016/S0008-6363(98)00013-3] [PMID: 9709409 ] 
[243] 
Furuno, T.; Yamasaki, F.; Yokoyama, T.; Sato, K.; Sato, T.; Doi, Y.; Sugiura, T. Effects of various doses of aspirin on platelet activity and endothelial function. Heart Vessels,  2011, 26(3), 267-273.
[http://dx.doi.org/10.1007/s00380-010-0054-8] [PMID: 21063876 ] 
[244] 
Duffy, S.J.; Tran, B.T.; New, G.; Tudball, R.N.; Esler, M.D.; Harper, R.W.; Meredith, I.T. Continuous release of vasodilator prostanoids contributes to regulation of resting forearm blood flow in humans. Am. J. Physiol.,  1998, 274(4), H1174-H1183.
[PMID: 9575920 ] 
[245] 
Nagelschmitz, J.; Blunck, M.; Kraetzschmar, J.; Ludwig, M.; Wensing, G.; Hohlfeld, T. Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous and oral administration to healthy volunteers. Clin. Pharmacol.,  2014, 6, 51-59.
[http://dx.doi.org/10.2147/CPAA.S47895] [PMID: 24672263 ] 
[246] 
Mitchell, J.A.; Akarasereenont, P.; Thiemermann, C.; Flower, R.J.; Vane, J.R. Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. Proc. Natl. Acad. Sci. USA,  1993, 90(24), 11693-11697.
[http://dx.doi.org/10.1073/pnas.90.24.11693] [PMID: 8265610 ] 
[247] 
Hennekens, C.H.; Schneider, W.R.; Pokov, A.; Hetzel, S.; Demets, D.; Serebruany, V.; Schröder, H. A randomized trial of aspirin at clinically relevant doses and nitric oxide formation in humans. J. Cardiovasc. Pharmacol. Ther.,  2010, 15(4), 344-348.
[http://dx.doi.org/10.1177/1074248410375091] [PMID: 20938039 ] 
[248] 
Hetzel, S.; DeMets, D.; Schneider, R.; Borzak, S.; Schneider, W.; Serebruany, V.; Schröder, H.; Hennekens, C.H. Aspirin increases nitric oxide formation in chronic stable coronary disease. J. Cardiovasc. Pharmacol. Ther.,  2013, 18(3), 217-221.
[http://dx.doi.org/10.1177/1074248413482753] [PMID: 23524841 ] 
[249] 
Geppert, A.; Graf, S.; Beckmann, R.; Hornykewycz, S.; Schuster, E.; Binder, B.R.; Huber, K. Concentration of endogenous tPA antigen in coronary artery disease: relation to thrombotic events, aspirin treatment, hyperlipidemia, and multivessel disease. Arterioscler. Thromb. Vasc. Biol.,  1998, 18(10), 1634-1642.
[http://dx.doi.org/10.1161/01.ATV.18.10.1634] [PMID: 9763537 ] 
[250] 
Vlachopoulos, C.; Aznaouridis, K.; Bratsas, A.; Ioakeimidis, N.; Dima, I.; Xaplanteris, P.; Stefanadis, C.; Tousoulis, D. Arterial stiffening and systemic endothelial activation induced by smoking: The role of COX-1 and COX-2. Int. J. Cardiol.,  2015, 189, 293-298.
[http://dx.doi.org/10.1016/j.ijcard.2015.04.029] [PMID: 25919966 ] 
[251] 
Kharbanda, R.K.; Walton, B.; Allen, M.; Klein, N.; Hingorani, A.D.; MacAllister, R.J.; Vallance, P. Prevention of inflammation-induced endothelial dysfunction: a novel vasculo-protective action of aspirin. Circulation,  2002, 105(22), 2600-2604.
[http://dx.doi.org/10.1161/01.CIR.0000017863.52347.6C] [PMID: 12045164 ] 
[252] 
Lou, J.; Povsic, T.J.; Allen, J.D.; Adams, S.D.; Myles, S.; Starr, A.Z.; Ortel, T.L.; Becker, R.C. The effect of aspirin on endothelial progenitor cell biology: preliminary investigation of novel properties. Thromb. Res.,  2010, 126(3), e175-e179.
[http://dx.doi.org/10.1016/j.thromres.2009.11.017] [PMID: 20659762 ] 
[253] 
Ueno, H.; Koyama, H.; Mima, Y.; Fukumoto, S.; Tanaka, S.; Shoji, T.; Emoto, M.; Shoji, T.; Nishizawa, Y.; Inaba, M. Comparison of the effect of cilostazol with aspirin on circulating endothelial progenitor cells and small-dense LDL cholesterol in diabetic patients with cerebral ischemia: a randomized controlled pilot trial. J. Atheroscler. Thromb.,  2011, 18(10), 883-890.
[http://dx.doi.org/10.5551/jat.9225] [PMID: 21701082 ] 
[254] 
Jiang, X.L.; Samant, S.; Lesko, L.J.; Schmidt, S. Clinical pharmacokinetics and pharmacodynamics of clopidogrel. Clin. Pharmacokinet.,  2015, 54(2), 147-166.
[http://dx.doi.org/10.1007/s40262-014-0230-6] [PMID: 25559342 ] 
[255] 
Cerda, A.; Pavez, M.; Manriquez, V.; Luchessi, A.D.; Leal, P.; Benavente, F.; Fajardo, C.M.; Salazar, L.; Hirata, M.H.; Hirata, R.D.C. Effects of clopidogrel on inflammatory cytokines and adhesion molecules in human endothelial cells: Role of nitric oxide mediating pleiotropic effects. Cardiovasc. Ther.,  2017, 35(4)
[http://dx.doi.org/10.1111/1755-5922.12261] [PMID: 28371087 ] 
[256] 
Ziemianin, B.; Olszanecki, R.; Uracz, W.; Marcinkiewicz, E.; Gryglewski, R.J. Thienopyridines: effects on cultured endothelial cells. J. Physiol. Pharmacol.,  1999, 50(4), 597-604.
[PMID: 10639010 ] 
[257] 
Yang, H.; Zhao, P.; Tian, S. Clopidogrel protects endothelium by hindering TNFα-induced VCAM-1 expression through CaMKKβ/AMPK/Nrf2 Pathway. J. Diabetes Res.,  2016, 20169128050
[http://dx.doi.org/10.1155/2016/9128050] [PMID: 26824050 ] 
[258] 
Hamilos, M.; Muller, O.; Ntalianis, A.; Trana, C.; Bartunek, J.; Sarno, G.; Mangiacapra, F.; Dierickx, K.; Meeus, P.; Cuisset, T.; De Bruyne, B.; Wijns, W.; Barbato, E. Relationship between peripheral arterial reactive hyperemia and residual platelet reactivity after 600 mg clopidogrel. J. Thromb. Thrombolysis,  2011, 32(1), 64-71.
[http://dx.doi.org/10.1007/s11239-011-0557-x] [PMID: 21290254 ] 
[259] 
Heitzer, T.; Rudolph, V.; Schwedhelm, E.; Karstens, M.; Sydow, K.; Ortak, M.; Tschentscher, P.; Meinertz, T.; Böger, R.; Baldus, S. Clopidogrel improves systemic endothelial nitric oxide bioavailability in patients with coronary artery disease: evidence for antioxidant and antiinflammatory effects. Arterioscler. Thromb. Vasc. Biol.,  2006, 26(7), 1648-1652.
[http://dx.doi.org/10.1161/01.ATV.0000225288.74170.dc] [PMID: 16675725 ] 
[260] 
Patti, G.; Grieco, D.; Dicuonzo, G.; Pasceri, V.; Nusca, A.; Di Sciascio, G. High versus standard clopidogrel maintenance dose after percutaneous coronary intervention and effects on platelet inhibition, endothelial function, and inflammation results of the ARMYDA-150 mg (antiplatelet therapy for reduction of myocardial damage during angioplasty) randomized study. J. Am. Coll. Cardiol.,  2011, 57(7), 771-778.
[http://dx.doi.org/10.1016/j.jacc.2010.09.050] [PMID: 21310311 ] 
[261] 
Warnholtz, A.; Ostad, M.A.; Velich, N.; Trautmann, C.; Schinzel, R.; Walter, U.; Munzel, T. A single loading dose of clopidogrel causes dose-dependent improvement of endothelial dysfunction in patients with stable coronary artery disease: results of a double-blind, randomized study. Atherosclerosis,  2008, 196(2), 689-695.
[http://dx.doi.org/10.1016/j.atherosclerosis.2006.12.009] [PMID: 17214996 ] 
[262] 
Willoughby, S.R.; Luu, L.J.; Cameron, J.D.; Nelson, A.J.; Schultz, C.D.; Worthley, S.G.; Worthley, M.I. Clopidogrel improves microvascular endothelial function in subjects with stable coronary artery disease. Heart Lung Circ.,  2014, 23(6), 534-541.
[http://dx.doi.org/10.1016/j.hlc.2014.01.005] [PMID: 24529502 ] 
[263] 
Ostad, M.A.; Nick, E.; Paixao-Gatinho, V.; Schnorbus, B.; Schiewe, R.; Tschentscher, P.; Munzel, T.; Warnholtz, A. Lack of evidence for pleiotropic effects of clopidogrel on endothelial function and inflammation in patients with stable coronary artery disease: results of the double-blind, randomized CASSANDRA study. Clin. Res. Cardiol.,  2011, 100(1), 29-36.
[http://dx.doi.org/10.1007/s00392-010-0199-6] [PMID: 20644943 ] 
[264] 
Ramadan, R.; Dhawan, S.S.; Syed, H.; Pohlel, F.K.; Binongo, J.N.; Ghazzal, Z.B.; Quyyumi, A.A. Effects of clopidogrel therapy on oxidative stress, inflammation, vascular function, and progenitor cells in stable coronary artery disease. J. Cardiovasc. Pharmacol.,  2014, 63(4), 369-374.
[http://dx.doi.org/10.1097/FJC.0000000000000057] [PMID: 24336012 ] 
[265] 
Woo, J.S.; Kim, W.; Jang, H.H.; Kim, J.B.; Kim, W.S.; Kim, K.S. Effect of platelet reactivity, endothelial function, and inflammatory status on outcomes in patients with stable angina pectoris on clopidogrel therapy. Am. J. Cardiol.,  2014, 113(5), 786-792.
[http://dx.doi.org/10.1016/j.amjcard.2013.11.025] [PMID: 24388620 ] 
[266] 
Campo, G.; Vieceli Dalla Sega, F.; Pavasini, R.; Aquila, G.; Gallo, F.; Fortini, F.; Tonet, E.; Cimaglia, P.; Del Franco, A.; Pestelli, G.; Pecoraro, A.; Contoli, M.; Balla, C.; Biscaglia, S.; Rizzo, P.; Ferrari, R. Biological effects of ticagrelor over clopidogrel in patients with stable coronary artery disease and chronic obstructive pulmonary disease. Thromb. Haemost.,  2017, 117(6), 1208-1216.
[http://dx.doi.org/10.1160/TH16-12-0973] [PMID: 28331925 ] 
[267] 
Mangiacapra, F.; Panaioli, E.; Colaiori, I.; Ricottini, E.; Lauria Pantano, A.; Pozzilli, P.; Barbato, E.; Di Sciascio, G. Clopidogrel versus ticagrelor for antiplatelet maintenance in diabetic patients treated with percutaneous coronary intervention: results of the clotildia study (clopidogrel high dose versus ticagrelor for antiplatelet maintenance in diabetic patients). Circulation,  2016, 134(11), 835-837.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.116.023743] [PMID: 27619717 ] 
[268] 
Zhang, Y.Z.; Chen, B.L.; Zhang, W.; Cao, X. Non-antiplatelet effect of clopidogrel: improving endothelial function in Chinese healthy subjects with different CYP2C19 genotype. Clin. Exp. Pharmacol. Physiol.,  2015, 42(1), 22-26.
[http://dx.doi.org/10.1111/1440-1681.12325] [PMID: 25311974 ] 
[269] 
Kwong, W.; Parker, J.D. The Effect of Clopidogrel on the response to ischemia reperfusion. J. Cardiovasc. Pharmacol. Ther.,  2017, 22(4), 368-373.
[http://dx.doi.org/10.1177/1074248416683047] [PMID: 28587582 ] 
[270] 
Watanabe, T.; Barker, T.A.; Berk, B.C. Angiotensin II and the endothelium: diverse signals and effects. Hypertension,  2005, 45(2), 163-169.
[http://dx.doi.org/10.1161/01.HYP.0000153321.13792.b9] [PMID: 15630047 ] 
[271] 
Daemen, M.J.; Lombardi, D.M.; Bosman, F.T.; Schwartz, S.M. Angiotensin II induces smooth muscle cell proliferation in the normal and injured rat arterial wall. Circ. Res.,  1991, 68(2), 450-456.
[http://dx.doi.org/10.1161/01.RES.68.2.450] [PMID: 1991349 ] 
[272] 
Griendling, K.K.; Minieri, C.A.; Ollerenshaw, J.D.; Alexander, R.W. Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ. Res.,  1994, 74(6), 1141-1148.
[http://dx.doi.org/10.1161/01.RES.74.6.1141] [PMID: 8187280 ] 
[273] 
Fleming, I. Signaling by the angiotensin-converting enzyme. Circ. Res.,  2006, 98(7), 887-896.
[http://dx.doi.org/10.1161/01.RES.0000217340.40936.53] [PMID: 16614314 ] 
[274] 
Murphey, L.J.; Malave, H.A.; Petro, J.; Biaggioni, I.; Byrne, D.W.; Vaughan, D.E.; Luther, J.M.; Pretorius, M.; Brown, N.J. Bradykinin and its metabolite bradykinin 1-5 inhibit thrombin-induced platelet aggregation in humans. J. Pharmacol. Exp. Ther.,  2006, 318(3), 1287-1292.
[http://dx.doi.org/10.1124/jpet.106.104026] [PMID: 16772538 ] 
[275] 
Brown, N.J.; Gainer, J.V.; Murphey, L.J.; Vaughan, D.E. Bradykinin stimulates tissue plasminogen activator release from human forearm vasculature through B(2) receptor-dependent, NO synthase-independent, and cyclooxygenase-independent pathway. Circulation,  2000, 102(18), 2190-2196.
[http://dx.doi.org/10.1161/01.CIR.102.18.2190] [PMID: 11056091 ] 
[276] 
Cheetham, C.; O’Driscoll, G.; Stanton, K.; Taylor, R.; Green, D. Losartan, an angiotensin type I receptor antagonist, improves conduit vessel endothelial function in Type II diabetes. Clin. Sci. (Lond.),  2001, 100(1), 13-17.
[PMID: 11115412  ] 
[277] 
Pelliccia, F.; Pasceri, V.; Cianfrocca, C.; Vitale, C.; Speciale, G.; Gaudio, C.; Rosano, G.M.; Mercuro, G. Angiotensin II receptor antagonism with telmisartan increases number of endothelial progenitor cells in normotensive patients with coronary artery disease: a randomized, double-blind, placebo-controlled study. Atherosclerosis,  2010, 210(2), 510-515.
[http://dx.doi.org/10.1016/j.atherosclerosis.2009.12.005] [PMID: 20044087 ] 
[278] 
Warnholtz, A.; Ostad, M.A.; Heitzer, T.; Thuneke, F.; Fröhlich, M.; Tschentscher, P.; Schwedhelm, E.; Böger, R.; Meinertz, T.; Munzel, T. AT1-receptor blockade with irbesartan improves peripheral but not coronary endothelial dysfunction in patients with stable coronary artery disease. Atherosclerosis,  2007, 194(2), 439-445.
[http://dx.doi.org/10.1016/j.atherosclerosis.2006.08.034] [PMID: 16970950 ] 
[279] 
Yilmaz, M.I.; Carrero, J.J.; Martín-Ventura, J.L.; Sonmez, A.; Saglam, M.; Celik, T.; Yaman, H.; Yenicesu, M.; Eyileten, T.; Moreno, J.A.; Egido, J.; Blanco-Colio, L.M. Combined therapy with renin-angiotensin system and calcium channel blockers in type 2 diabetic hypertensive patients with proteinuria: effects on soluble TWEAK, PTX3, and flow-mediated dilation. Clin. J. Am. Soc. Nephrol.,  2010, 5(7), 1174-1181.
[http://dx.doi.org/10.2215/CJN.01110210] [PMID: 20430947 ] 
[280] 
Takiguchi, S.; Ayaori, M.; Uto-Kondo, H.; Iizuka, M.; Sasaki, M.; Komatsu, T.; Takase, B.; Adachi, T.; Ohsuzu, F.; Ikewaki, K. Olmesartan improves endothelial function in hypertensive patients: link with extracellular superoxide dismutase. Hypertens. Res.,  2011, 34(6), 686-692.
[http://dx.doi.org/10.1038/hr.2011.11] [PMID: 21307868 ] 
[281] 
Sozen, A.B.; Kayacan, M.S.; Tansel, T.; Celebi, A.; Kudat, H.; Akkaya, V.; Erk, O.; Hatipoglu, I.; Demirel, S. Drugs with blocking effects on the renin-angiotensin-aldosterone system do not improve endothelial dysfunction long-term in hypertensive patients. J. Int. Med. Res.,  2009, 37(4), 996-1002.
[http://dx.doi.org/10.1177/147323000903700403] [PMID: 19761681 ] 
[282] 
Trevelyan, J.; Needham, E.W.; Morris, A.; Mattu, R.K. Comparison of the effect of enalapril and losartan in conjunction with surgical coronary revascularisation versus revascularisation alone on systemic endothelial function. Heart,  2005, 91(8), 1053-1057.
[http://dx.doi.org/10.1136/hrt.2004.036897] [PMID: 16020596 ] 
[283] 
Bahlmann, F.H.; de Groot, K.; Mueller, O.; Hertel, B.; Haller, H.; Fliser, D. Stimulation of endothelial progenitor cells: a new putative therapeutic effect of angiotensin II receptor antagonists. Hypertension,  2005, 45(4), 526-529.
[http://dx.doi.org/10.1161/01.HYP.0000159191.98140.89] [PMID: 15767470 ] 
[284] 
Tan, K.C.; Chow, W.S.; Ai, V.H.; Lam, K.S. Effects of angiotensin II receptor antagonist on endothelial vasomotor function and urinary albumin excretion in type 2 diabetic patients with microalbuminuria. Diabetes Metab. Res. Rev.,  2002, 18(1), 71-76.
[http://dx.doi.org/10.1002/dmrr.255] [PMID: 11921421 ] 
[285] 
Chung, N.A.; Beevers, D.G.; Lip, G. Effects of losartan versus hydrochlorothiazide on indices of endothelial damage/dysfunction, angiogenesis and tissue factor in essential hypertension. Blood Press.,  2004, 13(3), 183-189.
[http://dx.doi.org/10.1080/08037050410033312] [PMID: 15223728 ] 
[286] 
Bots, M.L.; Remme, W.J.; Lüscher, T.F.; Fox, K.M.; Bertrand, M.; Ferrari, R.; Simoons, M.L.; Grobbee, D.E. EUROPA-PERFECT Investigators. ACE inhibition and endothelial function: main findings of PERFECT, a sub-study of the EUROPA trial. Cardiovasc. Drugs Ther.,  2007, 21(4), 269-279.
[http://dx.doi.org/10.1007/s10557-007-6041-3] [PMID: 17657599 ] 
[287] 
Tikiz, C.; Utuk, O.; Pirildar, T.; Bayturan, O.; Bayindir, P.; Taneli, F.; Tikiz, H.; Tuzun, C. Effects of Angiotensin-converting enzyme inhibition and statin treatment on inflammatory markers and endothelial functions in patients with longterm rheumatoid arthritis. J. Rheumatol.,  2005, 32(11), 2095-2101.
[PMID: 16265685 ] 
[288] 
Mullen, M.J.; Clarkson, P.; Donald, A.E.; Thomson, H.; Thorne, S.A.; Powe, A.J.; Furuno, T.; Bull, T.; Deanfield, J.E. Effect of enalapril on endothelial function in young insulin-dependent diabetic patients: a randomized, double-blind study. J. Am. Coll. Cardiol.,  1998, 31(6), 1330-1335.
[http://dx.doi.org/10.1016/S0735-1097(98)00099-0] [PMID: 9581728 ] 
[289] 
Shahin, Y.; Khan, J.A.; Samuel, N.; Chetter, I. Angiotensin converting enzyme inhibitors effect on endothelial dysfunction: a meta-analysis of randomised controlled trials. Atherosclerosis,  2011, 216(1), 7-16.
[http://dx.doi.org/10.1016/j.atherosclerosis.2011.02.044] [PMID: 21411098 ] 
[290] 
Li, S.; Wu, Y.; Yu, G.; Xia, Q.; Xu, Y. Angiotensin II receptor blockers improve peripheral endothelial function: a meta-analysis of randomized controlled trials. PLoS One,  2014, 9(3)e90217
[http://dx.doi.org/10.1371/journal.pone.0090217] [PMID: 24595033 ] 
[291] 
Chen, J.D.; Liu, M.; Chen, X.H.; Yang, Z.J. Effect of Angiotensin receptor blockers on flow-mediated vasodilation: a meta-analysis of randomized controlled trials. Cardiology,  2015, 131(2), 69-79.
[http://dx.doi.org/10.1159/000375259] [PMID: 25872009 ] 
[292] 
Ito, A.; Egashira, K.; Narishige, T.; Muramatsu, K.; Takeshita, A. Renin-angiotensin system is involved in the mechanism of increased serum asymmetric dimethylarginine in essential hypertension. Jpn. Circ. J.,  2001, 65(9), 775-778.
[http://dx.doi.org/10.1253/jcj.65.775] [PMID: 11548874 ] 
[293] 
Napoli, C.; Sica, V.; de Nigris, F.; Pignalosa, O.; Condorelli, M.; Ignarro, L.J.; Liguori, A. Sulfhydryl angiotensin-converting enzyme inhibition induces sustained reduction of systemic oxidative stress and improves the nitric oxide pathway in patients with essential hypertension. Am. Heart J.,  2004, 148(1)e5
[http://dx.doi.org/10.1016/j.ahj.2004.03.025] [PMID: 15215814 ] 
[294] 
Gamboa, J.L.; Pretorius, M.; Sprinkel, K.C.; Brown, N.J.; Ikizler, T.A. Angiotensin converting enzyme inhibition increases ADMA concentration in patients on maintenance hemodialysis--a randomized cross-over study. BMC Nephrol.,  2015, 16, 167.
[http://dx.doi.org/10.1186/s12882-015-0162-x] [PMID: 26494370 ] 
[295] 
Bella, A.J.; Deyoung, L.X.; Al-Numi, M.; Brock, G.B. Daily administration of phosphodiesterase type 5 inhibitors for urological and nonurological indications. Eur. Urol.,  2007, 52(4), 990-1005.
[http://dx.doi.org/10.1016/j.eururo.2007.06.048] [PMID: 17646047 ] 
[296] 
Kukreja, R.C.; Salloum, F.; Das, A.; Ockaili, R.; Yin, C.; Bremer, Y.A.; Fisher, P.W.; Wittkamp, M.; Hawkins, J.; Chou, E.; Kukreja, A.K.; Wang, X.; Marwaha, V.R.; Xi, L. Pharmacological preconditioning with sildenafil: Basic mechanisms and clinical implications. Vascul. Pharmacol.,  2005, 42(5-6), 219-232.
[http://dx.doi.org/10.1016/j.vph.2005.02.010] [PMID: 15922255 ] 
[297] 
Ghalayini, I.F. Nitric oxide-cyclic GMP pathway with some emphasis on cavernosal contractility. Int. J. Impot. Res.,  2004, 16(6), 459-469.
[http://dx.doi.org/10.1038/sj.ijir.3901256] [PMID: 15229623 ] 
[298] 
Santi, D.; Giannetta, E.; Isidori, A.M.; Vitale, C.; Aversa, A.; Simoni, M. Therapy of endocrine disease. Effects of chronic use of phosphodiesterase inhibitors on endothelial markers in type 2 diabetes mellitus: a meta-analysis. Eur. J. Endocrinol.,  2015, 172(3), R103-R114.
[http://dx.doi.org/10.1530/EJE-14-0700] [PMID: 25277671 ] 
[299] 
Aversa, A.; Vitale, C.; Volterrani, M.; Fabbri, A.; Spera, G.; Fini, M.; Rosano, G.M. Chronic administration of Sildenafil improves markers of endothelial function in men with Type 2 diabetes. Diabet. Med.,  2008, 25(1), 37-44.
[http://dx.doi.org/10.1111/j.1464-5491.2007.02298.x] [PMID: 18199130 ] 
[300] 
Desouza, C.; Parulkar, A.; Lumpkin, D.; Akers, D.; Fonseca, V.A. Acute and prolonged effects of sildenafil on brachial artery flow-mediated dilatation in type 2 diabetes. Diabetes Care,  2002, 25(8), 1336-1339.
[http://dx.doi.org/10.2337/diacare.25.8.1336] [PMID: 12145231 ] 
[301] 
Burnett, A.L.; Strong, T.D.; Trock, B.J.; Jin, L.; Bivalacqua, T.J.; Musicki, B. Serum biomarker measurements of endothelial function and oxidative stress after daily dosing of sildenafil in type 2 diabetic men with erectile dysfunction. J. Urol.,  2009, 181(1), 245-251.
[http://dx.doi.org/10.1016/j.juro.2008.09.005] [PMID: 19013603 ] 
[302] 
Aversa, A.; Greco, E.; Bruzziches, R.; Pili, M.; Rosano, G.; Spera, G. Relationship between chronic tadalafil administration and improvement of endothelial function in men with erectile dysfunction: a pilot study. Int. J. Impot. Res.,  2007, 19(2), 200-207.
[http://dx.doi.org/10.1038/sj.ijir.3901513] [PMID: 16943794 ] 
[303] 
Foresta, C.; Ferlin, A.; De Toni, L.; Lana, A.; Vinanzi, C.; Galan, A.; Caretta, N. Circulating endothelial progenitor cells and endothelial function after chronic Tadalafil treatment in subjects with erectile dysfunction. Int. J. Impot. Res.,  2006, 18(5), 484-488.
[http://dx.doi.org/10.1038/sj.ijir.3901465] [PMID: 16541115 ] 
[304] 
Giannetta, E.; Feola, T.; Gianfrilli, D.; Pofi, R.; Dall’Armi, V.; Badagliacca, R.; Barbagallo, F.; Lenzi, A.; Isidori, A.M. Is chronic inhibition of phosphodiesterase type 5 cardioprotective and safe? A meta-analysis of randomized controlled trials. BMC Med.,  2014, 12, 185.
[http://dx.doi.org/10.1186/s12916-014-0185-3] [PMID: 25330139 ] 
[305] 
Katz, S.D.; Balidemaj, K.; Homma, S.; Wu, H.; Wang, J.; Maybaum, S. Acute type 5 phosphodiesterase inhibition with sildenafil enhances flow-mediated vasodilation in patients with chronic heart failure. J. Am. Coll. Cardiol.,  2000, 36(3), 845-851.
[http://dx.doi.org/10.1016/S0735-1097(00)00790-7] [PMID: 10987609 ] 
[306] 
Hatzichristou, D.; Gambla, M.; Rubio-Aurioles, E.; Buvat, J.; Brock, G.B.; Spera, G.; Rose, L.; Lording, D.; Liang, S. Efficacy of tadalafil once daily in men with diabetes mellitus and erectile dysfunction. Diabet. Med.,  2008, 25(2), 138-146.
[http://dx.doi.org/10.1111/j.1464-5491.2007.02338.x] [PMID: 18290855 ] 
[307] 
Foresta, C.; De Toni, L.; Di Mambro, A.; Garolla, A.; Ferlin, A.; Zuccarello, D. The PDE5 inhibitor sildenafil increases circulating endothelial progenitor cells and CXCR4 expression. J. Sex. Med.,  2009, 6(2), 369-372.
[http://dx.doi.org/10.1111/j.1743-6109.2008.01014.x] [PMID: 18823318  ] 
[308] 
Gori, T.; Sicuro, S.; Dragoni, S.; Donati, G.; Forconi, S.; Parker, J.D. Sildenafil prevents endothelial dysfunction induced by ischemia and reperfusion via opening of adenosine triphosphate-sensitive potassium channels: a human in vivo study. Circulation,  2005, 111(6), 742-746.
[http://dx.doi.org/10.1161/01.CIR.0000155252.23933.2D] [PMID: 15699265 ] 
[309] 
Kimura, M.; Higashi, Y.; Hara, K.; Noma, K.; Sasaki, S.; Nakagawa, K.; Goto, C.; Oshima, T.; Yoshizumi, M.; Chayama, K. PDE5 inhibitor sildenafil citrate augments endothelium-dependent vasodilation in smokers. Hypertension,  2003, 41(5), 1106-1110.
[http://dx.doi.org/10.1161/01.HYP.0000068202.42431.CC] [PMID: 12695418 ] 
[310] 
McLaughlin, K.; Lytvyn, Y.; Luca, M.C.; Liuni, A.; Gori, T.; Parker, J.D. Repeated daily dosing with sildenafil provides sustained protection from endothelial dysfunction caused by ischemia and reperfusion: a human in vivo study. Am. J. Physiol. Heart Circ. Physiol.,  2014, 307(6), H888-H894.
[http://dx.doi.org/10.1152/ajpheart.00215.2014] [PMID: 25063793 ] 
[311] 
La Vignera, S.; Condorelli, R.; Vicari, E.; D’Agata, R.; Calogero, A.E. Circulating endothelial progenitor cells and endothelial microparticles in patients with arterial erectile dysfunction and metabolic syndrome. J. Androl.,  2012, 33(2), 202-209.
[http://dx.doi.org/10.2164/jandrol.111.013136] [PMID: 21474787 ] 
[312] 
Dishy, V.; Harris, P.A.; Pierce, R.; Prasad, H.C.; Sofowora, G.; Bonar, H.L.; Wood, A.J.; Stein, C.M. Sildenafil does not improve nitric oxide-mediated endothelium-dependent vascular responses in smokers. Br. J. Clin. Pharmacol.,  2004, 57(2), 209-212.
[http://dx.doi.org/10.1046/j.1365-2125.2003.01974.x] [PMID: 14748820 ] 
[313] 
Dishy, V.; Sofowora, G.; Harris, P.A.; Kandcer, M.; Zhan, F.; Wood, A.J.; Stein, C.M. The effect of sildenafil on nitric oxide-mediated vasodilation in healthy men. Clin. Pharmacol. Ther.,  2001, 70(3), 270-279.
[http://dx.doi.org/10.1067/mcp.2001.117995] [PMID: 11557915 ] 
[314] 
Robinson, S.D.; Ludlam, C.A.; Boon, N.A.; Newby, D.E. Phosphodiesterase type 5 inhibition does not reverse endothelial dysfunction in patients with coronary heart disease. Heart,  2006, 92(2), 170-176.
[http://dx.doi.org/10.1136/hrt.2004.059683] [PMID: 15863522 ] 
[315] 
Konstantinopoulos, A.; Giannitsas, K.; Athanasopoulos, A.; Spathas, D.; Perimenis, P. The impact of daily sildenafil on levels of soluble molecular markers of endothelial function in plasma in patients with erectile dysfunction. Expert Opin. Pharmacother.,  2009, 10(2), 155-160.
[http://dx.doi.org/10.1517/14656560802678211] [PMID: 19236190 ] 
[316] 
Kambayashi, J.; Liu, Y.; Sun, B.; Shakur, Y.; Yoshitake, M.; Czerwiec, F. Cilostazol as a unique antithrombotic agent. Curr. Pharm. Des.,  2003, 9(28), 2289-2302.
[http://dx.doi.org/10.2174/1381612033453910] [PMID: 14529391 ] 
[317] 
Goto, S. Cilostazol: potential mechanism of action for antithrombotic effects accompanied by a low rate of bleeding. Atheroscler. Suppl.,  2005, 6(4), 3-11.
[http://dx.doi.org/10.1016/j.atherosclerosissup.2005.09.002] [PMID: 16275169 ] 
[318] 
Hashimoto, A.; Miyakoda, G.; Hirose, Y.; Mori, T. Activation of endothelial nitric oxide synthase by cilostazol via a cAMP/protein kinase A- and phosphatidylinositol 3-kinase/Akt-dependent mechanism. Atherosclerosis,  2006, 189(2), 350-357.
[http://dx.doi.org/10.1016/j.atherosclerosis.2006.01.022] [PMID: 16545819 ] 
[319] 
Hashimoto, A.; Tanaka, M.; Takeda, S.; Ito, H.; Nagano, K. Cilostazol induces PGI2 production via activation of the downstream Epac-1/Rap1 signaling cascade to increase intracellular calcium by PLCε and to activate p44/42 MAPK in human aortic endothelial cells. PLoS One,  2015, 10(7)e0132835
[http://dx.doi.org/10.1371/journal.pone.0132835] [PMID: 26181635 ] 
[320] 
Hattori, Y.; Suzuki, K.; Tomizawa, A.; Hirama, N.; Okayasu, T.; Hattori, S.; Satoh, H.; Akimoto, K.; Kasai, K. Cilostazol inhibits cytokine-induced nuclear factor-kappaB activation via AMP-activated protein kinase activation in vascular endothelial cells. Cardiovasc. Res.,  2009, 81(1), 133-139.
[http://dx.doi.org/10.1093/cvr/cvn226] [PMID: 18703532 ] 
[321] 
Chuang, S.Y.; Yang, S.H.; Pang, J.H. Cilostazol reduces MCP-1-induced chemotaxis and adhesion of THP-1 monocytes by inhibiting CCR2 gene expression. Biochem. Biophys. Res. Commun.,  2011, 411(2), 402-408.
[http://dx.doi.org/10.1016/j.bbrc.2011.06.163] [PMID: 21756880 ] 
[322] 
Suzuki, K.; Uchida, K.; Nakanishi, N.; Hattori, Y. Cilostazol activates AMP-activated protein kinase and restores endothelial function in diabetes. Am. J. Hypertens.,  2008, 21(4), 451-457.
[http://dx.doi.org/10.1038/ajh.2008.6] [PMID: 18369362 ] 
[323] 
Kim, M.J.; Lee, J.H.; Park, S.Y.; Hong, K.W.; Kim, C.D.; Kim, K.Y.; Lee, W.S. Protection from apoptotic cell death by cilostazol, phosphodiesterase type III inhibitor, via cAMP-dependent protein kinase activation. Pharmacol. Res.,  2006, 54(4), 261-267.
[http://dx.doi.org/10.1016/j.phrs.2006.05.006] [PMID: 16822680 ] 
[324] 
Chao, T.H.; Chen, I.C.; Lee, C.H.; Chen, J.Y.; Tsai, W.C.; Li, Y.H.; Tseng, S.Y.; Tsai, L.M.; Tseng, W.K. Cilostazol enhances mobilization of circulating endothelial progenitor cells and improves endothelium-dependent function in patients at high risk of cardiovascular disease. Angiology,  2016, 67(7), 638-646.
[http://dx.doi.org/10.1177/0003319715606249] [PMID: 27401788 ] 
[325] 
Lee, S.J.; Lee, J.S.; Choi, M.H.; Lee, S.E.; Shin, D.H.; Hong, J.M. Cilostazol improves endothelial function in acute cerebral ischemia patients: a double-blind placebo controlled trial with flow-mediated dilation technique. BMC Neurol.,  2017, 17(1), 169.
[http://dx.doi.org/10.1186/s12883-017-0950-y] [PMID: 28851320 ] 
[326] 
Mori, H.; Maeda, A.; Wakabayashi, K.; Sato, T.; Sasai, M.; Tashiro, K.; Iso, Y.; Ebato, M.; Suzuki, H. The effect of cilostazol on endothelial function as assessed by flow-mediated dilation in patients with coronary artery disease. J. Atheroscler. Thromb.,  2016, 23(10), 1168-1177.
[http://dx.doi.org/10.5551/jat.32912] [PMID: 27169919  ] 
[327] 
Kim, K.S.; Park, H.S.; Jung, I.S.; Park, J.H.; Ahn, K.T.; Jin, S.A.; Park, Y.K.; Kim, J.H.; Lee, J.H.; Choi, S.W.; Jeong, J.O.; Seong, I.W. Endothelial dysfunction in the smokers can be improved with oral cilostazol treatment. J. Cardiovasc. Ultrasound,  2011, 19(1), 21-25.
[http://dx.doi.org/10.4250/jcu.2011.19.1.21] [PMID: 21519488 ] 
[328] 
Oida, K.; Ebata, K.; Kanehara, H.; Suzuki, J.; Miyamori, I. Effect of cilostazol on impaired vasodilatory response of the brachial artery to ischemia in smokers. J. Atheroscler. Thromb.,  2003, 10(2), 93-98.
[http://dx.doi.org/10.5551/jat.10.93] [PMID: 12740483 ] 
[329] 
Jeong, I.S.; Park, J.H.; Jin, S.A.; Kim, J.H.; Lee, J.H.; Choi, S.W.; Jeong, J.O.; Seong, I.W. Oral sarpogrelate can improve endothelial dysfunction as effectively as oral cilostazol, with fewer headaches, in active young male smokers. Heart Vessels,  2013, 28(5), 578-582.
[http://dx.doi.org/10.1007/s00380-012-0282-1] [PMID: 22968852 ] 
[330] 
Rajagopalan, S.; Pfenninger, D.; Somers, E.; Kehrer, C.; Chakrabarti, A.; Mukherjee, D.; Brook, R.; Kaplan, M.J. Effects of cilostazol in patients with Raynaud’s syndrome. Am. J. Cardiol.,  2003, 92(11), 1310-1315.
[http://dx.doi.org/10.1016/j.amjcard.2003.08.013] [PMID: 14636909 ] 
Rights & Permissions Print Cite
Article Metrics
81
2
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/0929867326666190119154152	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
当代药物化学

内皮作为糖尿病的治疗靶点：从基本机制到临床实践

摘要

Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.

Approaches to the treatment of chronic inflammation

Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications

Chalcogen-modified nucleic acid analogues

当代药物化学

内皮作为糖尿病的治疗靶点：从基本机制到临床实践

摘要

Call for Papers in Thematic Issues

Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.

Approaches to the treatment of chronic inflammation

Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications

Chalcogen-modified nucleic acid analogues

Related Journals

Related Books

Related Articles
