Abstract 882: Prokineticin/EG-VEGF receptor-1 Promotes Cardiomyocyte Survival and angiogenesis
Myocardial infarction is the major cause of death in industrial countries. Identification of novel factors that promote cardiomyocyte survival and repair, is therefore of high interest. Prokineticins are potent angiogenic and hematopoietic factors that bind to two G protein-coupled receptors (GPCRs) to initiate their biological effects. Since prokineticin receptor-1 (PKR1) expression is substantially changed in the ischemic mouse and human hearts, we investigated the contribution of this receptor to recovery of myocardial ischemic injury. Using the coronary ligation-mouse model of myocardial infarction, we show that transient PKR1 gene transfer reduces mortality and preserves left ventricular function by reduced cardiac apoptosis and enhanced capillary vascularization without altering VEGF levels. Stimulation of PKR1 activates Akt to protect the cardiomyocytes against hypoxic insult, and induces tube-like formation in cultured endothelial cells. In contrast, transgene-mediated overexpression of PKR1 in mouse cardiomyocytes leads to increased capillary density and VEGF expression in the heart, indicating that cardiomyocyte-derived VEGF is involved in PKR1-mediated vascularization in non-ischemic heart. These data suggest that PKR1 could serve as a novel therapeutic target.