A step closer to unravel the mystery of myocyte self-regeneration during cardiac hypertrophy

posted Jan 25, 2017, 10:38 PM by sourav ghosh
Sagartirtha Sarkar
Professor, Genetics and Molecular Cardiology Laboratory, Department of Zoology, University of Calcutta, India

Cardiac hypertrophy leading to heart failure is one of the major causes of mortality worldwide that is triggered by nitrosative stress mediated apoptosis of terminally differentiated cardiomyocytes. S- nitrosylation of NEMO was studied in regulation of myocyte fate during cardiac hypertrophy. Myocyte targeted overexpression of S-nitrosyl mutants of NEMO in renal artery ligated rats showed significant downregulation of hypertrophy marker genes and betterment of cardiac function. S-nitrosyl mutants of NEMO showed downregulation of apoptotic potential of myocytes along with excess nuclear translocation of p65 protein within these cells during hypertrophy. Our lab earlier showed downregulation of p65 during regression of hypertrophy as a concomitant effect of reduced apoptotic load in cardiomyocytes. However, S-nitrosyl mutants of NEMO showed constitutive activation of p65 even when apoptotic load was lowered during regression of hypertrophy, thus inducing a subset of genes involved in cellular proliferation that shifted the balance towards regeneration of terminally differentiated cardiomyocytes and subsequent improvement in cardiac function. Thus, introducing S-nitrosyl mutants of NEMO in pathological cardiac microenvironment promises to be a potential tool for damaged tissue engineering via regeneration of quiescent myocyte population.