51 ANTI-INFLAMMATORY EFFECTS OF A HIGH-DENSITY LIPOPROTEIN MIMETIC PEPTIDE, D-4F, ON ARTERIAL WALLS

Cardiovascular disease, caused mainly by atherosclerosis, kills more people in the United States than cancer, pulmonary disease, and accidents combined. Atherosclerosis is the build-up of cholesterol, lipids, and concomitant inflammation leading to progressive narrowing of the vessel walls. LDL-derived oxidized phospholipids, such as 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (Ox-PAPC), cause inflammation of arterial wall and promote atherosclerosis. D-4F is an 18-amino acid peptide with physiochemical similarities to one of the functionally important proteins in HDL, apolipoprotein A-I. This peptide has been shown in vivo to be very promising in reducing inflammation and promoting reverse cholesterol transport. The goal of this project is to test whether D-4F inhibits the inflammation caused by Ox-PAPC in vitro on human aortic endothelial cells (HAECs). HAECs were treated with Ox-PAPC with and without D-4F for 4 hours at 37°C. Cellular RNA was isolated and inflammatory cytokines (ie, IL-8) were quantified by real-time PCR. Preliminary results showed a 50% inhibition by D-4F (100 ng/mL) on the inflammation induced by Ox-PAPC (15 μg/mL) and HDL (10 μg/mL). HDL appears to be necessary for D-4F to inhibit the inflammation, and the unexpected inflammation induced by HDL may be due to proinflammatory HDL. These data suggest that D-4F can prevent the inflammatory response evoked by Ox-PAPC and is a step toward preventing atherosclerosis. Delineating its mechanism may provide a better understanding of how to reverse atherosclerosis and possibly prevent many ischemic heart attacks.