Cardiovascular disease (CVD) is the leading cause of death world-wide. Hypertension is a major risk factor for CVD. The renin-angiotensin system (RAS) is one of the most important systems regulating blood pressure. In this project, we found (pro)renin receptor [(P)RR], a RAS component, has a novel RAS independent role in regulating lipid metabolism in vivo. Moreover, we have identified megalin as a novel endocytic receptor for prorenin and renin, and that the (P)RR determines its activity. Further, we investigated the placental RAS in preeclampsia, and explored the role of proton pump inhibitor in regulating megalin-mediated renin internalization. Finally, we uncovered that the angiotensinogen siRNA is a novel blood pressure-lowering tool.

A.H.J. Danser (Jan) , X. Lu (Xifeng)
Erasmus University Rotterdam
Division of Pharmacology and Vascular Medicine