Non-FAU Project
Start date : 01.01.2016
End date : 31.12.2019
Pathological myocardial hypertrophy is a maladaptive process occurring in response to an increased cardiac workload [1, 2]. Left ventricular hypertrophy (LVH) is the single most important predictor of premature cardiovascular death in the Framingham risk assessment. In addition, it is a major risk factor for various cardiac arrhythmias, such as atrial fibrillation, the most common significant cardiac rhythm disturbance. The members of a TRPC subfamily of transient receptor potential (TRP)-type ion channels, TRPC3 and TRPC6, have been implicated in development of the cardiac hypertrophy and progression to heart failure [3, 4]. This project will test the hypothesis that cardiac pressure-overload instigates a stretch-mediated up-regulation of cardiac TRPC3 and TRPC6 ion channels, leading to Ca2+ entry, which activates a signaling cascade involving Ca2+/calmodulin-dependent protein kinase II (CaMKII)/histone deacetylase 4 (HDAC4)/myocyte enhancer factor-2 (MEF2) to induce hypertrophy and associated arrhythmias.