Cardiac Dys-Synchronization and Arrhythmia in Hyperhomocysteinemia

Karni   S.   Moshal; Clacy   K.   Camel; Ganesh   K.   Kartha; Mesia   M.   Steed; Neetu      Tyagi; Utpal      Sen; Y.   James   Kang; David      Lominadze; Claudio      Maldonado; Suresh   C.   Tyagi

Abstract

Although cardiac synchronization is important in maintaining myocardial performance, the mechanism of dys-synchronization in ailing to failing myocardium is unclear. It is known that the cardiac myocyte contracts and relaxes individually; however, it synchronizes only when connected to one another by low resistance communications called gap junction protein (connexins) and extra cellular matrix (ECM). Therefore, the remodeling of connexins and ECM in heart failure plays an important role in cardiac conduction, synchronization and arrhythmias. This review for the first time addresses the role of systemic accumulation of homocysteine (Hcy) in vasospasm, pressure and volume overload heart failure, hypertension and cardiac arrhythmias. The attenuation of calcium-dependent mitochondrial (mt), endothelial and neuronal nitric oxide synthase (mtNOS, eNOS and nNOS) by Hcy plays a significant role in cardiac arrhythmias. The signal transduction mechanisms in Hcy-induced matrix metalloproteinase (MMP) activation in cardiac connexin remodeling are discussed.

Keywords: Heart failure, calpain, hypertension, vascular remodeling, ECM, calcium channel, tachycardia, bradycardia, arrhythmia, LVH