Prolylcarboxypeptidase Promotes Endothelial Cell Proliferation and Vascular Repair

Abstract 1142 Background. The S28 serine protease, prolylcarboxypeptidase (PRCP) degrades bradykinin, angiotensin II, alpha melanocyte stimulating hormone and actives plasma prekallikrein. Additionally our studies indicate that PRCP depletions in vivo and in cultured cells are associated with increased reactive oxygen species (ROS) and loss of constitutive anticoagulant function of endothelium (Blood 2011; 117:3929). PRCP-depleted mice are prothrombotic and hypertensive. We observed that PRCP-depleted cells in culture have reduced growth. We posited that PRCP promotes vascular health by influencing cell proliferation, angiogenesis, and wound repair. Methods and Results. Initial investigations determined that PRCP influences vascular endothelial cell proliferation. Bovine aortic endothelial cells (BAEC) were depleted of PRCP by siRNA knockdown resulting in 5% residual mRNA. After transfecting equal numbers of BAEC, at 24 h, the PRCP siRNA transfected cells have reduced proliferation, −18±3 change in cells/high power field (HPF) (mean±SEM), compared to the sham transfected cells, +23±8 cells/HPF, p Conclusions. These combined studies indicate that PRCP levels in endothelial cells influence cell proliferation and growth. In the whole animal this cell biology observation translates into less induced and wound repair angiogenesis. Since PRCP-depleted endothelial cells and vessels from PRCPgt/gt have increased ROS with loss of anticoagulant properties and PRCPgt/gt have higher thrombosis risk, the finding that PRCP also influences endothelial cell growth and angiogenesis suggests that PRCP promotes vascular health and injury repair. Disclosures: No relevant conflicts of interest to declare.