Hyperhomocysteinemia and sudden cardiac death: potential arrhythmogenic mechanisms.
Elevated levels of serum homocysteine (Hcy) resulting in hyperhomocysteinemia (HHcy) have been implicated in cardiac pathological conditions including: coronary heart disease (CHD), acute myocardial infarction, arrhythmogenesis and sudden cardiac death (SCD). The mechanisms by which HHcy leads to arrhythmogenesis and SCD are unknown. Novel findings indicate that Hcy is an agonist of the N-methyl-D-aspartate receptor (NMDA-R), known to be present in cardiac tissue, and when activated, increases intracellular calcium leading to increased cell excitability. Also, HHcy induces oxidative stress in cardiac cells and activates matrix metalloproteinases (MMPs) that degrade cell membranes and proteins. Here we review the literature relevant to HHcy-induced oxidative stress leading to cardiac tissue remodelling that may adversely affect cell-to-cell impulse conduction, in particular on the heart's specialized conduction system, and may provide substrate for arrhythmogenesis and SCD. Efficacy of B vitamin supplementation in patient populations with HHcy and CHD is also reviewed.
Maldonado
Claudio
C
Department of Physiology and Biophysics, and Department of Surgery, University of Louisville, Louisville, KY 40292, USA. cjmald01@louisville.edu
Soni
Chirag V
CV
Todnem
Nathan D
ND
Pushpakumar
Sathnur
S
Rosenberger
Dorothea
D
Givvimani
Srikanth
S
Villafane
Juan
J
Tyagi
Suresh C
SC
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000503:physiopathology* / Q000517:prevention & control; D020013:Calcium Signaling / Q000502:physiology; D017630:Connexins / Q000502:physiology; D003327:Coronary Disease / Q000628:therapy; D016757:Death, Sudden, Cardiac / Q000209:etiology* / Q000517:prevention & control; D019587:Dietary Supplements; D006321:Heart / Q000503:physiopathology; D006329:Heart Conduction System / Q000503:physiopathology; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists; D012307:Risk Factors; D014803:Vitamin B Complex / Q000627:therapeutic use
D017630:Connexins; D016194:Receptors, N-Methyl-D-Aspartate; D006710:Homocysteine; D014803:Vitamin B Complex; D020782:Matrix Metalloproteinases