HETEROCHROMATIN REMODELLING IN CARDIAC HYPERTROPHY

Abstract

The reversibility of LVH and its corresponding gene expression upon ventricular off-loading by medical treatment or by the implantation of left ventricular assist devices implies a level of cardiac plasticity in the cardiac chromatin. Reports have pointed to epigenetic mechanisms which mediate the heart failure stress-gene response, targeting histone methylation (heterochromatin) for hypertrophy reversal however remains untested. We sought to determine the reversibility in H3K27me3 heterochromatin remodeling in the progression of LVH and to assess its role in pathological cardiac remodeling. We studied the reversibility of LVH achieved by the release of transverse aortic constriction (TAC), and GSKJ4 (H3K27me3 demethylase inhibitor) treatment on TAC mice. Our results show a role for reversible heterochromatin remodeling in targeting the treatment of cardiac hypertrophy, and propose a novel mechanism for H3K27me3 demethylases in gene expression reprogramming involved in cardiac hypertrophy. Targeting H3K27me3 heterochromatin may offer new options for heart disease therapeutics.