Abstract P294: Cardiomyocyte-Specific RBPJ Regulates Angiogenesis and Stress Response in the Adult Heart

Regulation of adult myocardial angiogenesis is critical for an appropriate cardiac function. We found that lack of RBPJ on isolated mouse adult cardiomyocytes increases angiogenic factors gene expresion and promoter hyperacetylation and hypermethylation of Notch target gene promoters (HEY2) and angiogenic factors. Accordingly, cardiomyocyte specific RBPJ KO adult mice show a denser microvasculature. RBPJ KO mice suggest an angiogenesis repressive role of RBPJ during homeostasis. Stress induced by myocardial infarction (MI) or cardiac overload (TAC) activate an angiogenic response to compensate the increased oxygen demand. We have found that Notch pathway is activated and RBPJ accumulated in the nucleus after MI and TAC. On isolated mouse adult cardiomyocytes, RBPJ is also able to control angiogenesis by mediating a hypoxia-induced response independent of Notch receptor activation. Mice lacking RBPJ in cardiomyocytes present a blunted angiogenic response. Suprisingly RBPJ KO mice had a better cardiac performance alter MI. We propose that RBPJ is a critical effector of the hypoxic response in the heart and the mechanisms by which RBPJ KO could protect from injury will be discussed on the presentation.