Protease Activity in Atherosclerotic Plaque Formation and Protection by Novel HDL-targeting Protease Inhibitors

This projects focuses on inflammation in the artery wall in atherosclerotic cardiovascular disease. We are studying how high density lipoprotein (HDL) particles transport anti-inflammatory proteins from the circulation to the subendothelial space where plaques occur. Our goal is to test the hypothesis that HDL can carry protease inhibitor proteins across vascular endothelial cells where they can suppress proteolytic activity and resulting inflammation. We will test this using cell culture based experiments and mouse models of atherosclerosis. Human HDL will be isolated from plasma and enriched with recombinant protease inhibitor proteins for transcytosis and atherosclerosis protection experiments. Additionally, a novel class of HDL-targeting protease inhibitors will be evaluated for their ability to prevent atherosclerosis in mouse models.