title: Asymmetric Dimethylarginine (ADMA): a promising biomarker for cardiovascular disease?
abstract: Asymmetric Dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) production. ADMA is generated from methylation of arginine residues by protein arginine methyltransferases (PRMTs) and subsequent proteolysis, while its elimination is achieved mainly by degradation with dimethylarginine dimethylaminohydrolase (DDAH). Oxidative stress, endothelial nitric oxide synthase (eNOS) inhibition, eNOS uncoupling, inflammation and shear stress play a pivotal role in ADMA pathophysiology by managing PRMT/DDAH expression and NO synthesis and leading to a common result - endothelial dysfunction. Endothelial dysfunction seems to be the common finding in studies investigating the role of ADMA in cardiovascular disease (CVD). High-performance liquid chromatography (HPLC), mass spectrometry (MS) and enzyme-linked immunosorbent assay (ELISA) are the existing methods for ADMA quantification. However, none of them fulfils all the criteria to be characterized as "gold standard". ADMA is significantly associated with risk factors for CVD and almost with every disease of the cardiovascular system; showing an independent, strong prognostic value for mortality and future cardiovascular events. This article aims to review the current knowledge about ADMA biology and metabolism, pathophysiological mechanisms implicating ADMA in CVD, methods for the determination of ADMA and its association with CVD risk factors and established CVDs.
authors.affiliation: Cardiology Department and Cardiac Catheterization Laboratory, Athens General Hospital G. Gennimatas, Athens, Greece. bourasgio@gmail.com
authors.forename: Georgios
authors.initials: G
authors.lastname: Bouras
authors.forename: Spyridon
authors.initials: S
authors.lastname: Deftereos
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tousoulis
authors.forename: Georgios
authors.initials: G
authors.lastname: Giannopoulos
authors.forename: Georgios
authors.initials: G
authors.lastname: Chatzis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tsounis
authors.forename: Michael W
authors.initials: MW
authors.lastname: Cleman
authors.forename: Christodoulos
authors.initials: C
authors.lastname: Stefanadis
mesh_terms: D000375:Aging; D000581:Amidohydrolases / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000503:physiopathology*; D002561:Cerebrovascular Disorders / Q000378:metabolism / Q000503:physiopathology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D048909:Diabetes Complications / Q000378:metabolism / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D012016:Reference Values; D012307:Risk Factors; D012907:Smoking
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D000581:Amidohydrolases; C059999:dimethylargininase