Influence of HDL-cholesterol-elevating drugs on the in vitro activity of the HDL receptor SR-BI

• DOI: 10.1194/jlr.m700209-jlr200
• Publication Date: 2007-05-29T00:34:35Z
• Authors: Thomas J.F. Nieland; Jared T. Shaw; Firoz A. Jaipuri; Zoltan Maliga; Jay L. Duffner; Angela N. Koehler; Monty Krieger
• Keywords: Scavenger Receptor; Fenofibrate; Clofibrate; Gemfibrozil; Bezafibrate; Niacin; Clofibric acid; Reverse cholesterol transport

Treatment of atherosclerotic disease often focuses on reducing plasma LDL-cholesterol or increasing HDL-cholesterol. We examined in vitro the effects HDL receptor [scavenger class B type I (SR-BI)] activity three classes clinical and experimental HDL-cholesterol-elevating compounds: niacin, fibrates, HDL376. Fenofibrate (FF) HDL376 were potent (IC(50) approximately 1 microM), direct inhibitors SR-BI-mediated lipid transport cells liposomes reconstituted with purified SR-BI. FF, a prodrug, was more inhibitor SR-BI than an activator peroxisome proliferator-activated alpha, target its active fenofibric acid (FFA) derivative. Nevertheless, FFA, four other fibrates (clofibrate, gemfibrozil, ciprofibrate, bezafibrate), niacin had little, if any, effect SR-BI, suggesting that they do not directly vivo. However, similarities treatment gene knockout metabolism vivo (increased HDL-cholesterol particle sizes) structure-activity relationship analysis suggest may be help elucidate function diverse mammalian models determine therapeutic potential SR-BI-directed pharmaceuticals.