Ion channel determinants of cardiac hypertrophy and cardiomyopathy

Abstract

The work presented in this dissertation address the role of two ion channels; TRPV1 and CRACM1, and the serine protease, Corin, in the progression of pressure-overload cardiac hypertrophy. Results show that the absence of TRPV1 in vivo is protective against cardiac hypertrophy under conditions of pressure overload (Chapter 2); however, in the absence of CRACM1 the pathology is exacerbated (Chapter 3). Further, mice lacking a gene disrupting Corin show an immediate and severe hypertrophic response (Chapter 4). Lastly, follow up studies with a TRPV1 blocker have proved effective in suppressing the progression of cardiac hypertrophy under conditions of pressure overload (Chapter 5). The results from this dissertation, for the first time, show that in vivo TRPV1 is a key player and therapeutic target in cardiac hypertrophy, CRACM1 plays an important protective role and Corin is necessary for the heart to compensate under conditions of pressure overload.