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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Review Article

Role of Hydrogen in Atherosclerotic Disease: From Bench to Bedside

Author(s): Shucun Qin *

Volume 27, Issue 5, 2021

Published on: 24 November, 2020

Page: [713 - 722] Pages: 10

DOI: 10.2174/1381612826666201124112152

Price: $65

Abstract

Atherosclerotic cardiovascular and cerebrovascular diseases are among the leading causes of morbidity and mortality worldwide. Given our recent understanding of its role as a small-molecule antioxidant and anti- inflammatory agent, hydrogen may play an important role in preventing and treating atherosclerotic cardiovascular and cerebrovascular disease. In the past decade, more than 50 publications in the English language literature considered the role of hydrogen as an anti-atherosclerotic agent. In this review, we summarized the pathophysiological characteristics and risk factors associated with atherosclerosis (AS) and the laboratory research data that focuses on hydrogen to prevent and treat this condition, including the responses observed in both animal models and human studies. We will also consider the molecular mechanisms underlying the efficacy of hydrogen molecules with respect to atherosclerotic disease. Future studies might include clinical trials with larger sample populations as well as experiments designed to explore the molecular mechanisms associated with hydrogen treatment in greater depth.

Keywords: Atherosclerosis, cardiovascular diseases, hydrogen, efficacy response, treatment, prevention, oxidative stress.

« Previous Next »
[1]
Herrington W, Lacey B, Sherliker P, Armitage J, Lewington S. Epidemiology of Atherosclerosis and the Potential to Reduce the Global Burden of Atherothrombotic Disease. Circ Res 2016; 118(4): 535-46.
[http://dx.doi.org/10.1161/CIRCRESAHA.115.307611] [PMID: 26892956]
[2]
Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA 2002; 287: 2570-81.
[http://dx.doi.org/10.1001/jama.287.19.2570]
[3]
Weber C, Noels H. Atherosclerosis: current pathogenesis and therapeutic options. Nat Med 2011; 17(11): 1410-22.
[http://dx.doi.org/10.1038/nm.2538] [PMID: 22064431]
[4]
Glass CK, Witztum JL. Atherosclerosis. The road ahead. Cell 2001; 104(4): 503-16.
[http://dx.doi.org/10.1016/S0092-8674(01)00238-0] [PMID: 11239408]
[5]
Falk E. Pathogenesis of atherosclerosis. J Am Coll Cardiol 2006; 47(8)(Suppl.): C7-C12.
[http://dx.doi.org/10.1016/j.jacc.2005.09.068] [PMID: 16631513]
[6]
Sharrett AR, Ballantyne CM, Coady SA, et al. Atherosclerosis Risk in Communities Study Group Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: The Atherosclerosis Risk in Communities (ARIC) Study. Circulation 2001; 104(10): 1108-13.
[http://dx.doi.org/10.1161/hc3501.095214] [PMID: 11535564]
[7]
Khera AV, Emdin CA, Drake I, et al. Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease. N Engl J Med 2016; 375(24): 2349-58.
[http://dx.doi.org/10.1056/NEJMoa1605086] [PMID: 27959714]
[8]
Förstermann U, Xia N, Li H. Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circ Res 2017; 120(4): 713-35.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.309326] [PMID: 28209797]
[9]
Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 2002; 105(9): 1135-43.
[http://dx.doi.org/10.1161/hc0902.104353] [PMID: 11877368]
[10]
Bäck M, Yurdagul A Jr, Tabas I, Öörni K, Kovanen PT. Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities. Nat Rev Cardiol 2019; 16(7): 389-406.
[http://dx.doi.org/10.1038/s41569-019-0169-2] [PMID: 30846875]
[11]
Gimbrone MA Jr, García-Cardeña G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ Res 2016; 118(4): 620-36.
[http://dx.doi.org/10.1161/CIRCRESAHA.115.306301] [PMID: 26892962]
[12]
Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation 2004; 109(23)(Suppl. 1): III27-32.
[http://dx.doi.org/10.1161/01.CIR.0000131515.03336.f8] [PMID: 15198963]
[13]
Song G, Lin Q, Zhao H, et al. Hydrogen activates ATP-binding cassette transporter A1-dependent efflux ex vivo and improves high-density lipoprotein function in patients with hypercholesterolemia: a double-blinded, randomized, and placebo-controlled trial. J Clin Endocrinol Metab 2015; 100(7): 2724-33.
[http://dx.doi.org/10.1210/jc.2015-1321] [PMID: 25978109]
[14]
Nakao A, Toyoda Y, Sharma P, Evans M, Guthrie N. Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study. J Clin Biochem Nutr 2010; 46(2): 140-9.
[http://dx.doi.org/10.3164/jcbn.09-100] [PMID: 20216947]
[15]
Zong C, Song G, Yao S, et al. Administration of hydrogen-saturated saline decreases plasma low-density lipoprotein cholesterol levels and improves high-density lipoprotein function in high-fat diet-fed hamsters. Metabolism 2012; 61(6): 794-800.
[http://dx.doi.org/10.1016/j.metabol.2011.10.014] [PMID: 22153840]
[16]
Song G, Li M, Sang H, et al. Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome. J Lipid Res 2013; 54(7): 1884-93.
[http://dx.doi.org/10.1194/jlr.M036640] [PMID: 23610159]
[17]
Korovljev D, Trivic T, Drid P, Ostojic SM. Molecular hydrogen affects body composition, metabolic profiles, and mitochondrial function in middle-aged overweight women. Ir J Med Sci 2018; 187(1): 85-9.
[http://dx.doi.org/10.1007/s11845-017-1638-4] [PMID: 28560519]
[18]
Kajiyama S, Hasegawa G, Asano M, et al. Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutr Res 2008; 28(3): 137-43.
[http://dx.doi.org/10.1016/j.nutres.2008.01.008] [PMID: 19083400]
[19]
Shirahata S, Hamasaki T, Haramaki K, et al. Anti-diabetes effect of water containing hydrogen molecule and Pt nanoparticles. BMC Proc 2011; 5(Suppl. 8): 18.
[http://dx.doi.org/10.1186/1753-6561-5-S8-P18]
[20]
Kamimura N, Nishimaki K, Ohsawa I, Ohta S. Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db/db mice. Obesity (Silver Spring) 2011; 19(7): 1396-403.
[http://dx.doi.org/10.1038/oby.2011.6] [PMID: 21293445]
[21]
Wang QJ, Zha XJ, Kang ZM, Xu MJ, Huang Q, Zou DJ. Therapeutic effects of hydrogen saturated saline on rat diabetic model and insulin resistant model via reduction of oxidative stress. Chin Med J (Engl) 2012; 125(9): 1633-7.
[PMID: 22800834]
[22]
Amitani H, Asakawa A, Cheng K, et al. Hydrogen improves glycemic control in type1 diabetic animal model by promoting glucose uptake into skeletal muscle [published correction appears in PLoS One 2013; 8(4)
[23]
Zhang X, Liu J, Jin K, et al. Subcutaneous injection of hydrogen gas is a novel effective treatment for type 2 diabetes. J Diabetes Investig 2018; 9(1): 83-90.
[http://dx.doi.org/10.1111/jdi.12674] [PMID: 28390099]
[24]
Ning Y, Shang Y, Huang H, et al. Attenuation of cigarette smoke-induced airway mucus production by hydrogen-rich saline in rats. PLoS One 2013; 8(12)e83429
[http://dx.doi.org/10.1371/journal.pone.0083429] [PMID: 24376700]
[25]
Zong C, Song G, Yao S, et al. Cigarette smoke exposure impairs reverse cholesterol transport which can be minimized by treatment of hydrogen-saturated saline. Lipids Health Dis 2015; 14: 159.
[http://dx.doi.org/10.1186/s12944-015-0160-9] [PMID: 26634341]
[26]
Liu X, Ma C, Wang X, et al. Hydrogen coadministration slows the development of COPD-like lung disease in a cigarette smoke-induced rat model. Int J Chron Obstruct Pulmon Dis 2017; 12: 1309-24.
[http://dx.doi.org/10.2147/COPD.S124547] [PMID: 28496315]
[27]
Lu W, Li D, Hu J, et al. Hydrogen gas inhalation protects against cigarette smoke-induced COPD development in mice. J Thorac Dis 2018; 10(6): 3232-43.
[http://dx.doi.org/10.21037/jtd.2018.05.93] [PMID: 30069319]
[28]
Liu Z, Geng W, Jiang C, et al. Hydrogen-rich saline inhibits tobacco smoke-induced chronic obstructive pulmonary disease by alleviating airway inflammation and mucus hypersecretion in rats. Exp Biol Med (Maywood) 2017; 242(15): 1534-41.
[http://dx.doi.org/10.1177/1535370217725249] [PMID: 28795606]
[29]
Wang Y, Jing L, Zhao XM, et al. Protective effects of hydrogen-rich saline on monocrotaline-induced pulmonary hypertension in a rat model. Respir Res 2011; 12: 26.
[http://dx.doi.org/10.1186/1465-9921-12-26] [PMID: 21375753]
[30]
He B, Zhang Y, Kang B, Xiao J, Xie B, Wang Z. Protection of oral hydrogen water as an antioxidant on pulmonary hypertension. Mol Biol Rep 2013; 40(9): 5513-21.
[http://dx.doi.org/10.1007/s11033-013-2653-9] [PMID: 23955545]
[31]
Kishimoto Y, Kato T, Ito M, et al. Hydrogen ameliorates pulmonary hypertension in rats by anti-inflammatory and antioxidant effects. J Thorac Cardiovasc Surg 2015; 150(3): 645-54.e3.
[http://dx.doi.org/10.1016/j.jtcvs.2015.05.052] [PMID: 26095621]
[32]
Guan P, Lin XM, Yang SC, et al. Hydrogen gas reduces chronic intermittent hypoxia-induced hypertension by inhibiting sympathetic nerve activity and increasing vasodilator responses via the antioxidation. J Cell Biochem 2019; 120(3): 3998-4008.
[http://dx.doi.org/10.1002/jcb.27684] [PMID: 30259991]
[33]
Matsuoka H, Miyata S, Okumura N, et al. Hydrogen gas improves left ventricular hypertrophy in Dahl rat of salt-sensitive hypertension. Clin Exp Hypertens 2019; 41(4): 307-11.
[http://dx.doi.org/10.1080/10641963.2018.1481419] [PMID: 29902079]
[34]
Ohsawa I, Nishimaki K, Yamagata K, Ishikawa M, Ohta S. Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice. Biochem Biophys Res Commun 2008; 377(4): 1195-8.
[http://dx.doi.org/10.1016/j.bbrc.2008.10.156] [PMID: 18996093]
[35]
Song G, Tian H, Qin S, et al. Hydrogen decreases athero-susceptibility in apolipoprotein B-containing lipoproteins and aorta of apolipoprotein E knockout mice. Atherosclerosis 2012; 221(1): 55-65.
[http://dx.doi.org/10.1016/j.atherosclerosis.2011.11.043] [PMID: 22209213]
[36]
Ekuni D, Tomofuji T, Endo Y, et al. Hydrogen-rich water prevents lipid deposition in the descending aorta in a rat periodontitis model. Arch Oral Biol 2012; 57(12): 1615-22.
[http://dx.doi.org/10.1016/j.archoralbio.2012.04.013] [PMID: 22607937]
[37]
Iketani M, Sekimoto K, Igarashi T, et al. Administration of hydrogen-rich water prevents vascular aging of the aorta in LDL receptor-deficient mice. Sci Rep 2018; 8(1): 16822.
[http://dx.doi.org/10.1038/s41598-018-35239-0] [PMID: 30429524]
[38]
Song G, Zong C, Zhang Z, et al. Molecular hydrogen stabilizes atherosclerotic plaque in low-density lipoprotein receptor-knockout mice. Free Radic Biol Med 2015; 87: 58-68.
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.06.018] [PMID: 26117323]
[39]
Si Y, Tian H, Dong B, et al. Evaluation of Hydrogen-Rich Water as Adjuvant Treatment for Unstable Angina. The 6th National Conference on Hydrogen Medicine and Biology, Xi-An. China. 2019.
[40]
Ohsawa I, Ishikawa M, Takahashi K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 2007; 13(6): 688-94.
[http://dx.doi.org/10.1038/nm1577] [PMID: 17486089]
[41]
Tao G, Song G, Qin S. Molecular hydrogen: current knowledge on mechanism in alleviating free radical damage and diseases. Acta Biochim Biophys Sin (Shanghai) 2019; 51(12): 1189-97.
[http://dx.doi.org/10.1093/abbs/gmz121] [PMID: 31738389]
[42]
Qin ZX, Yu P, Qian DH, et al. Hydrogen-rich saline prevents neointima formation after carotid balloon injury by suppressing ROS and the TNF-α/NF-κB pathway. Atherosclerosis 2012; 220(2): 343-50.
[http://dx.doi.org/10.1016/j.atherosclerosis.2011.11.002] [PMID: 22153150]
[43]
Chen L, Ma C, Bian Y, et al. Hydrogen treatment protects mice against chronic pancreatitis by restoring regulatory T cells loss. Cell Physiol Biochem 2017; 44(5): 2005-16.
[http://dx.doi.org/10.1159/000485906] [PMID: 29237160]
[44]
Noda K, Tanaka Y, Shigemura N, et al. Hydrogen-supplemented drinking water protects cardiac allografts from inflammation-associated deterioration. Transpl Int 2012; 25(12): 1213-22.
[http://dx.doi.org/10.1111/j.1432-2277.2012.01542.x] [PMID: 22891787]
[45]
Itoh T, Hamada N, Terazawa R, et al. Molecular hydrogen inhibits lipopolysaccharide/interferon γ-induced nitric oxide production through modulation of signal transduction in macrophages. Biochem Biophys Res Commun 2011; 411(1): 143-9.
[http://dx.doi.org/10.1016/j.bbrc.2011.06.116] [PMID: 21723254]
[46]
Hara F, Tatebe J, Watanabe I, Yamazaki J, Ikeda T, Morita T. Molecular hydrogen alleviates cellular senescence in endothelial cells. Circ J 2016; 80(9): 2037-46.
[http://dx.doi.org/10.1253/circj.CJ-16-0227] [PMID: 27477846]
[47]
Song G, Tian H, Liu J, Zhang H, Sun X, Qin S. H2 inhibits TNF-α-induced lectin-like oxidized LDL receptor-1 expression by inhibiting nuclear factor κB activation in endothelial cells. Biotechnol Lett 2011; 33(9): 1715-22.
[http://dx.doi.org/10.1007/s10529-011-0630-8] [PMID: 21544615]
[48]
Sakai T, Sato B, Hara K, et al. Consumption of water containing over 3.5 mg of dissolved hydrogen could improve vascular endothelial function. Vasc Health Risk Manag 2014; 10: 591-7.
[PMID: 25378931]
[49]
Wang Y, Wu YP, Han JJ, et al. Inhibitory effects of hydrogen on in vitro platelet activation and in vivo prevention of thrombosis formation. Life Sci 2019; 233116700
[http://dx.doi.org/10.1016/j.lfs.2019.116700] [PMID: 31356907]
[50]
Liu BY, Qin SC. Different types of molecular hydrogen donors and their pharmacokinetics in vivo. Sheng Li Xue Bao 2019; 71(2): 371-7.
[PMID: 31008498]
[51]
Wu F, Qiu Y, Ye G, et al. Treatment with hydrogen molecule attenuates cardiac dysfunction in streptozotocin-induced diabetic mice. Cardiovasc Pathol 2015; 24(5): 294-303.
[http://dx.doi.org/10.1016/j.carpath.2015.04.008] [PMID: 25979689]
[52]
Guo J, Dong W, Jin L, Wang P, Hou Z, Zhang Y. Hydrogen-rich saline prevents bone loss in diabetic rats induced by streptozotocin. Int Orthop 2017; 41(10): 2119-28.
[http://dx.doi.org/10.1007/s00264-017-3581-4] [PMID: 28748382]
[53]
Chen S, Jiang W. Effect of hydrogen injected subcutaneously on testicular tissues of rats exposed to cigarette smoke. Int J Clin Exp Med 2015; 8(4): 5565-70.
[PMID: 26131139]
[54]
Chen X, Liu Q, Wang D, et al. Protective effects of hydrogen-rich saline on rats with smoke inhalation injury. Oxid Med Cell Longev 2015; 2015106836
[http://dx.doi.org/10.1155/2015/106836] [PMID: 26090070]

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