Novel molecular pathways in cardiac hypertrophy and failure

Coordinator:		Prof. Dr. med. Norbert Frey
Institution:		Abteilung Innere Medizin III, Uniklinik Heidelberg
Homepage:		www.klinikum.uni-heidelberg.de

Sustained myocardial hypertrophy can ultimately result in heart failure and sudden death. In an attempt to identify genetic modifiers of hypertrophy we have recently conducted 500k SNP analyses in 500 patients with left ventricular hypertrophy (LVH). Now, we aim to further characterize the LVH-associated genes on the molecular level, including gain of function and loss of function experiments in cultivated cardiomyocytes. Also, yeast two-hybrid screens with novel genes as “baits” will be performed to identify interacting proteins and the underlying molecular pathways. Moreover, we plan to perform a genome-wide siRNA screen for genes that modulate hypertrophic signalling using semi-automatical immunofluorescence assays. In complementary in vivo experiments, we plan to analyze several transgenic and knock-out animal models for cardiac hypertrophy and failure which have already been established, including two novel genes, termed CSEMP1 and CAMP1 which are associated with human heart failure. Utilizing this integrated approach of both human and experimental data, we aim to identify key pathways that are suitable as targets for novel treatment strategies.