Cardiac dys-synchronization and arrhythmia in hyperhomocysteinemia.
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.
Moshal
Karni S
KS
Department of Physiology and Biophysics, University of Louisville School of Medicine, Kentucky 40202, USA. suresh.tyagi@louisville.edu
Camel
Clacy K
CK
Kartha
Ganesh K
GK
Steed
Mesia M
MM
Tyagi
Neetu
N
Sen
Utpal
U
Kang
Y James
YJ
Lominadze
David
D
Maldonado
Claudio
C
Tyagi
Suresh C
SC
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000503:physiopathology; D006801:Humans; D020138:Hyperhomocysteinemia / Q000201:enzymology / Q000503:physiopathology*; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000502:physiology; D010084:Oxidation-Reduction; D015398:Signal Transduction / Q000502:physiology
D020782:Matrix Metalloproteinases