B04

We hypothesize and provide preliminary evidence that Smyd2 methyltransferase-driven non-histone protein (HIF-1α, p53, BMPR2) methylation underlie key pathological features of right ventricular remodeling. This project aims to further investigate the functional and causative role of Smyd2, HIF-1α, p53, and BMPR2 in cardiac endothelial cells and cardiomyocytes in experimental and clinical right ventricular hypertrophy. An established rAAV-associated cell specific gene delivery will be utilized in mice upon pulmonary artery banding. The ultimate goal of the project to investigate in detail the interplay of Smyd2/HIF1α/p53/BMPR2 and to decipher at the  molecular level Smyd2-driven mechanisms which are critical for the processes of RV remodeling such as capillarization, fibrosis and myocardial performance, aiming to develop novel treatment strategies.