title: Role of S-adenosylhomocysteine in cardiovascular disease and its potential epigenetic mechanism.
abstract: Transmethylation reactions utilize S-adenosylmethionine (SAM) as a methyl donor and are central to the regulation of many biological processes: more than fifty SAM-dependent methyltransferases methylate a broad spectrum of cellular compounds including DNA, histones, phospholipids and other small molecules. Common to all SAM-dependent transmethylation reactions is the release of the potent inhibitor S-adenosylhomocysteine (SAH) as a by-product. SAH is reversibly hydrolyzed to adenosine and homocysteine by SAH hydrolase. Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. However, a major unanswered question is if homocysteine is causally involved in disease pathogenesis or simply a passive and indirect indicator of a more complex mechanism. A chronic elevation in homocysteine levels results in a parallel increase in intracellular or plasma SAH, which is a more sensitive biomarker of cardiovascular disease than homocysteine and suggests that SAH is a critical pathological factor in homocysteine-associated disorders. Previous reports indicate that supplementation with folate and B vitamins efficiently lowers homocysteine levels but not plasma SAH levels, which possibly explains the failure of homocysteine-lowering vitamins to reduce vascular events in several recent clinical intervention studies. Furthermore, more studies are focusing on the role and mechanisms of SAH in different chronic diseases related to hyperhomocysteinemia, such as cardiovascular disease, kidney disease, diabetes, and obesity. This review summarizes the current role of SAH in cardiovascular disease and its effect on several related risk factors. It also explores possible the mechanisms, such as epigenetics and oxidative stress, of SAH. This article is part of a Directed Issue entitled: Epigenetic dynamics in development and disease.
authors.affiliation: Department of Nutrition and Food Hygiene, Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, China. Electronic address: xyjszcdc@163.com.
authors.forename: Yunjun
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: The Jockey Club School of Public Health and Primary Care, School of Public Health, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Xuefen
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Nutrition and Food Hygiene, Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Nutrition and Food Hygiene, Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
authors.forename: Jinzhou
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Nutrition and Food Hygiene, Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
authors.forename: Chaoqiong
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Nutrition and Food Hygiene, Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
authors.forename: Haixiong
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Nutrition and Food Hygiene, Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Nutrition and Food Hygiene, Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Huang
authors.affiliation: Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Xia
authors.affiliation: Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China. Electronic address: lingwenhua2012@163.com.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Ling
mesh_terms: D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D044127:Epigenesis, Genetic; D006801:Humans; D020138:Hyperhomocysteinemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D012435:S-Adenosylhomocysteine / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism
chemical_list: D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine
keywords: Atherosclerosis; Cardiovascular disease; Epigenetic; Homocysteine; S-adenosylhomocysteine