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Endocrine, Metabolic & Immune Disorders - Drug Targets

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ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

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Research Article

Calcium-Regulating Hormonal System and HMGB1 in Cardiomyopathies

Author(s): Knarik R. Harutyunyan, Hermine T. Abrahamyan, Satenik H. Adamyan, Souren Mkrtchian and Anna S. Ter-Markosyan*

Volume 23, Issue 1, 2023

Published on: 12 October, 2022

Page: [115 - 121] Pages: 7

DOI: 10.2174/1871530322666220817110538

Price: $65

Abstract

Background: Calcium ions play a key role in the heart's functional activity. The steadystate levels of calcium are contingent on the calcium regulating hormonal system, impairment of which might result in the development of cardiac pathology. An important role in these processes is also attributed to the specific inflammatory mediator, HMGB1, one of the damage-associated molecular patterns (DAMPs) released by immune cells or cell damage.

Objective: This study investigated the cardioprotective potential of the calcium-regulating hormonal system in cardiomyopathies with an emphasis on the possible role of HMGB1.

Methods: Ca2+ and inorganic phosphate levels were determined in the serum using an electrolyte analyzer and spectrophotometric analyzer correspondingly. The 1-34 fragment of parathyroid hormone (PTH), calcitonin, vitamin D, and HMGB1 were detected using ELISA kits.

Results: The levels of PTH, calcitonin, phosphate, and HMGB1 were found elevated in females suffering from cardiomyopathy. The same tendency was observed in men; however, statistically significant changes were registered only for PTH and phosphate.

Conclusion: It can be suggested that among other reasons, the decrease of the left ventricular function in cardiomyopathy patients can be linked to the high HMGB1, whereas the activation of the calciumregulating system as manifested by the elevated PTH aims at restoration of calcium homeostasis and thus have positive, i.e. cardioprotective consequences.

Keywords: Cardiomyopathy, calcium-regulating hormonal system, calcium, phosphate, parathyroid hormone, calcitonin, vitamin D, HMGB1.

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[1]
Schirone, L.; Forte, M.; Palmerio, S.; Yee, D.; Nocella, C.; Angelini, F.; Pagano, F.; Schiavon, S.; Bordin, A.; Carrizzo, A.; Vecchione, C.; Valenti, V.; Chimenti, I.; De Falco, E.; Sciarretta, S.; Frati, G. A review of the molecular mechanisms underlying the development and progression of cardiac remodeling. Oxid. Med. Cell. Longev., 2017, 2017, 3920195.
[http://dx.doi.org/10.1155/2017/3920195] [PMID: 28751931]
[2]
Dadson, K.; Hauck, L.; Billia, F. Molecular mechanisms in cardiomyopathy. Clin. Sci. (Lond.), 2017, 131(13), 1375-1392.
[http://dx.doi.org/10.1042/CS20160170] [PMID: 28645928]
[3]
Maron, B.J.; Towbin, J.A.; Thiene, G.; Antzelevitch, C.; Corrado, D.; Arnett, D.; Moss, A.J.; Seidman, C.E.; Young, J.B. Contemporary definitions and classification of the cardiomyopathies: An American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation, 2006, 113(14), 1807-1816.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.174287] [PMID: 16567565]
[4]
Wang, S.Q.; Song, L.S.; Lakatta, E.G.; Cheng, H. Ca2+ signalling between single L-type Ca2+ channels and ryanodine receptors in heart cells. Nature, 2001, 410(6828), 592-596.
[http://dx.doi.org/10.1038/35069083] [PMID: 11279498]
[5]
Levi, A.J.; Brooksby, P.; Hancox, J.C. One hump or two? The triggering of calcium release from the sarcoplasmic reticulum and the voltage dependence of contraction in mammalian cardiac muscle. Cardiovasc. Res., 1993, 27(10), 1743-1757.
[http://dx.doi.org/10.1093/cvr/27.10.1743] [PMID: 8275519]
[6]
Cleemann, L.; Morad, M. Role of Ca2+ channel in cardiac excitation-contraction coupling in the rat: Evidence from Ca2+ transients and contraction. J. Physiol., 1991, 432(1), 283-312.
[http://dx.doi.org/10.1113/jphysiol.1991.sp018385] [PMID: 1653321]
[7]
Palmeri, N.O.; Walker, M.D. Parathyroid hormone and cardiac electrophysiology: A review. Cardiol. Rev., 2019, 27(4), 182-188.
[http://dx.doi.org/10.1097/CRD.0000000000000250] [PMID: 31008771]
[8]
Jansen, J.; Gres, P.; Umschlag, C.; Heinzel, F.R.; Degenhardt, H.; Schluter, K.D.; Heusch, G.; Schulz, R. Parathyroid hormone-related peptide improves contractile function of stunned myocardium in rats and pigs. Am. J. Physiol. Heart Circ. Physiol., 2003, 284(1), H49-H55.
[http://dx.doi.org/10.1152/ajpheart.01037.2001] [PMID: 12485816]
[9]
Gruson, D.; Buglioni, A.; Burnett, J.C., Jr PTH: Potential role in management of heart failure. Clin. Chim. Acta, 2014, 433, 290-296.
[http://dx.doi.org/10.1016/j.cca.2014.03.029] [PMID: 24704306]
[10]
Tian, J.; Smogorzewski, M.; Kedes, L.; Massry, S.G. Parathyroid hormone-parathyroid hormone related protein receptor messenger RNA is present in many tissues besides the kidney. Am. J. Nephrol., 1993, 13(3), 210-213.
[http://dx.doi.org/10.1159/000168620] [PMID: 8213933]
[11]
Ureña, P.; Kong, X.F.; Abou-Samra, A.B.; Jüppner, H.; Kronenberg, H.M.; Potts, J.T., Jr; Segre, G.V. Parathyroid hormone (PTH)/PTH-related peptide receptor messenger ribonucleic acids are widely distributed in rat tissues. Endocrinology, 1993, 133(2), 617-623.
[http://dx.doi.org/10.1210/endo.133.2.8393771] [PMID: 8393771]
[12]
Asavarut, P.; Zhao, H.; Gu, J.; Ma, D. The role of HMGB1 in inflammation-mediated organ injury. Acta Anaesthesiol. Taiwan., 2013, 51(1), 28-33.
[http://dx.doi.org/10.1016/j.aat.2013.03.007] [PMID: 23711603]
[13]
Tzeng, H.P.; Fan, J.; Vallejo, J.G.; Dong, J.W.; Chen, X.; Houser, S.R.; Mann, D.L. Negative inotropic effects of high-mobility group box 1 protein in isolated contracting cardiac myocytes. Am. J. Physiol. Heart Circ. Physiol., 2008, 294(3), H1490-H1496.
[http://dx.doi.org/10.1152/ajpheart.00910.2007] [PMID: 18223193]
[14]
Lin, L.; Knowlton, A.A. Innate immunity and cardiomyocytes in ischemic heart disease. Life Sci., 2014, 100(1), 1-8.
[http://dx.doi.org/10.1016/j.lfs.2014.01.062] [PMID: 24486305]
[15]
Shauer, A.; Gotsman, I.; Keren, A.; Zwas, D.R.; Hellman, Y.; Durst, R.; Admon, D. Acute viral myocarditis: Current concepts in diagnosis and treatment. Isr. Med. Assoc. J., 2013, 15(3), 180-185.
[PMID: 23662385]
[16]
Mann, D.L. The emerging role of innate immunity in the heart and vascular system: For whom the cell tolls. Circ. Res., 2011, 108(9), 1133-1145.
[http://dx.doi.org/10.1161/CIRCRESAHA.110.226936] [PMID: 21527743]
[17]
Hagiwara, S.; Iwasaka, H.; Uchino, T.; Noguchi, T. High mobility group box 1 induces a negative inotropic effect on the left ventricle in an isolated rat heart model of septic shock: A pilot study. Circ. J., 2008, 72(6), 1012-1017.
[http://dx.doi.org/10.1253/circj.72.1012] [PMID: 18503231]
[18]
Hashimoto, K.; Nakagawa, Y.; Shibuya, T.; Satoh, H.; Ushijima, T.; Imai, S. Effects of parathyroid hormone and related polypeptides on the heart and coronary circulation of dogs. J. Cardiovasc. Pharmacol., 1981, 3(4), 668-676.
[http://dx.doi.org/10.1097/00005344-198107000-00002] [PMID: 6167798]
[19]
Nickols, G.A.; Nana, A.D.; Nickols, M.A.; DiPette, D.J.; Asimakis, G.K. Hypotension and cardiac stimulation due to the parathyroid hormone-related protein, humoral hypercalcemia of malignancy factor. Endocrinology, 1989, 125(2), 834-841.
[http://dx.doi.org/10.1210/endo-125-2-834] [PMID: 2752979]
[20]
Ogino, K.; Burkhoff, D.; Bilezikian, J.P. The hemodynamic basis for the cardiac effects of parathyroid hormone (PTH) and PTH-related protein. Endocrinology, 1995, 136(7), 3024-3030.
[http://dx.doi.org/10.1210/endo.136.7.7789328] [PMID: 7789328]
[21]
Ross, G.; Schlüter, K.D. Cardiac-specific effects of parathyroid hormone-related peptide: Modification by aging and hypertension. Cardiovasc. Res., 2005, 66(2), 334-344.
[http://dx.doi.org/10.1016/j.cardiores.2005.02.001] [PMID: 15820202]
[22]
Shan, J.; Pang, P.K.; Lin, H.C.; Yang, M.C. Cardiovascular effects of human parathyroid hormone and parathyroid hormone-related peptide. J. Cardiovasc. Pharmacol., 1994, 23(Suppl. 2), S38-S41.
[PMID: 7518545]
[23]
Tastan, I.; Schreckenberg, R.; Mufti, S.; Abdallah, Y.; Piper, H.M.; Schlüter, K.D. Parathyroid hormone improves contractile performance of adult rat ventricular cardiomyocytes at low concentrations in a non-acute way. Cardiovasc. Res., 2009, 82(1), 77-83.
[http://dx.doi.org/10.1093/cvr/cvp027] [PMID: 19168854]
[24]
Bhandari, B.; Quintanilla Rodriguez, B.S.; Masood, W. Ischemic Cardiomyopathy; StatPearls: Treasure Island, FL, 2021.
[25]
Basuyau, J.P.; Mallet, E.; Leroy, M.; Brunelle, P. Reference intervals for serum calcitonin in men, women, and children. Clin. Chem., 2004, 50(10), 1828-1830.
[http://dx.doi.org/10.1373/clinchem.2003.026963] [PMID: 15388660]
[26]
Muscogiuri, G.; Annweiler, C.; Duval, G.; Karras, S.; Tirabassi, G.; Salvio, G.; Balercia, G.; Kimball, S.; Kotsa, K.; Mascitelli, L.; Bhattoa, H.P.; Colao, A. Vitamin D and cardiovascular disease: From atherosclerosis to myocardial infarction and stroke. Int. J. Cardiol., 2017, 230, 577-584.
[http://dx.doi.org/10.1016/j.ijcard.2016.12.053] [PMID: 28043680]
[27]
Saponaro, F.; Marcocci, C.; Zucchi, R.; Prontera, C.; Clerico, A.; Scalese, M.; Frascarelli, S.; Saba, A.; Passino, C. Hypovitaminosis D in patients with heart failure: Effects on functional capacity and patients’ survival. Endocrine, 2017, 58(3), 574-581.
[http://dx.doi.org/10.1007/s12020-017-1282-9] [PMID: 28337657]
[28]
Fitzpatrick, L.A.; Bilezikian, J.P.; Silverberg, S.J. Parathyroid hormone and the cardiovascular system. Curr. Osteoporos. Rep., 2008, 6(2), 77-83.
[http://dx.doi.org/10.1007/s11914-008-0014-8] [PMID: 18778568]
[29]
Grandi, N.C.; Brenner, H.; Hahmann, H.; Wüsten, B.; März, W.; Rothenbacher, D.; Breitling, L.P. Calcium, phosphate and the risk of cardiovascular events and all-cause mortality in a population with stable coronary heart disease. Heart, 2012, 98(12), 926-933.
[http://dx.doi.org/10.1136/heartjnl-2011-300806] [PMID: 22301505]
[30]
Loncar, G.; Bozic, B.; Cvetinovic, N.; Dungen, H.D.; Lainscak, M.; von Haehling, S.; Doehner, W.; Radojicic, Z.; Putnikovic, B.; Trippel, T.; Popovic, V. Secondary hyperparathyroidism prevalence and prognostic role in elderly males with heart failure. J. Endocrinol. Invest., 2017, 40(3), 297-304.
[http://dx.doi.org/10.1007/s40618-016-0561-2] [PMID: 27738907]
[31]
Brown, S.J.; Ruppe, M.D.; Tabatabai, L.S. The parathyroid gland and heart disease. Methodist DeBakey Cardiovasc. J., 2017, 13(2), 49-54.
[http://dx.doi.org/10.14797/mdcj-13-2-49] [PMID: 28740581]
[32]
Brunner, S.; Weinberger, T.; Huber, B.C.; Segeth, A.; Zaruba, M.M.; Theiss, H.D.; Assmann, G.; Herbach, N.; Wanke, R.; Mueller-Hoecker, J.; Franz, W.M. The cardioprotective effects of parathyroid hormone are independent of endogenous granulocyte-colony stimulating factor release. Cardiovasc. Res., 2012, 93(2), 330-339.
[http://dx.doi.org/10.1093/cvr/cvr303] [PMID: 22080594]
[33]
Adamyan, S.H.; Harutyunyan, K.R.; Abrahamyan, H.T.; Khudaverdyan, D.N.; Mkrtchian, S.; Ter-Markosyan, A.S. Can the calcium-regulating hormones counteract the detrimental impact of pro-inflammatory damage-associated molecular patterns in the development of heart failure? J. Investig. Med., 2021, 69(6), 1148-1152.
[http://dx.doi.org/10.1136/jim-2020-001754] [PMID: 33952612]
[34]
Centeno, P.P.; Herberger, A.; Mun, H.C.; Tu, C.; Nemeth, E.F.; Chang, W.; Conigrave, A.D.; Ward, D.T. Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion. Nat. Commun., 2019, 10(1), 4693.
[http://dx.doi.org/10.1038/s41467-019-12399-9] [PMID: 31619668]
[35]
Su, F.F.; Shi, M.Q.; Guo, W.G.; Liu, X.T.; Wang, H.T.; Lu, Z.F.; Zheng, Q.S. High-mobility group box 1 induces calcineurin-mediated cell hypertrophy in neonatal rat ventricular myocytes. Mediators Inflamm., 2012, 2012, 805149.
[http://dx.doi.org/10.1155/2012/805149] [PMID: 22778498]
[36]
Zhang, C.; Mo, M.; Ding, W.; Liu, W.; Yan, D.; Deng, J.; Luo, X.; Liu, J. High-Mobility Group Box 1 (HMGB1) impaired cardiac excitation-contraction coupling by enhancing the Sarcoplasmic Reticulum (SR) Ca2+ leak through TLR4-ROS signaling in cardiomyocytes. J. Mol. Cell. Cardiol., 2014, 74, 260-273.
[http://dx.doi.org/10.1016/j.yjmcc.2014.06.003] [PMID: 24937603]
[37]
Qi, Y.; Goel, R.; Kim, S.; Richards, E.M.; Carter, C.S.; Pepine, C.J.; Raizada, M.K.; Buford, T.W. Intestinal permeability biomarker zonulin is elevated in healthy aging. J. Am. Med. Dir. Assoc., 2017, 18, 810-e814.
[http://dx.doi.org/10.1016/j.jamda.2017.05.018]
[38]
Le, Y.; Wang, Y.; Zhou, L.; Xiong, J.; Tian, J.; Yang, X.; Gai, X.; Sun, Y. Cigarette smoke-induced HMGB1 translocation and release contribute to migration and NF-κB activation through inducing autophagy in lung macrophages. J. Cell. Mol. Med., 2020, 24(2), 1319-1331.
[http://dx.doi.org/10.1111/jcmm.14789] [PMID: 31769590]
[39]
Fonken, L.K.; Frank, M.G.; Kitt, M.M.; D’Angelo, H.M.; Norden, D.M.; Weber, M.D.; Barrientos, R.M.; Godbout, J.P.; Watkins, L.R.; Maier, S.F. The alarmin HMGB1 mediates age-induced neuroinflammatory priming. J. Neurosci., 2016, 36(30), 7946-7956.
[http://dx.doi.org/10.1523/JNEUROSCI.1161-16.2016] [PMID: 27466339]
[40]
Chen, L.; Zhu, H.; Su, S.; Harshfield, G.; Sullivan, J.; Webb, C.; Blumenthal, J.A.; Wang, X.; Huang, Y.; Treiber, F.A.; Kapuku, G.; Li, W.; Dong, Y. High-mobility group box-1 Is associated with obesity, inflammation, and subclinical cardiovascular risk among young adults: A longitudinal cohort study. Arterioscler. Thromb. Vasc. Biol., 2020, 40(11), 2776-2784.
[http://dx.doi.org/10.1161/ATVBAHA.120.314599] [PMID: 32814439]
[41]
Andersson, U.; Ottestad, W.; Tracey, K.J. Extracellular HMGB1: A therapeutic target in severe pulmonary inflammation including COVID-19? Mol. Med., 2020, 26(1), 42.
[http://dx.doi.org/10.1186/s10020-020-00172-4] [PMID: 32380958]

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