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J Lipid Res DOI:10.1194/jlr.M700209-JLR200

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

Publication TypeJournal Article
Year of Publication2007
AuthorsNieland, TJF, Shaw, JT, Jaipuri, FA, Maliga, Z, Duffner, JL, Koehler, AN, Krieger, M
JournalJ Lipid Res
Date Published2007 Aug
KeywordsAnticholesteremic Agents, Cells, Cultured, Cholesterol, HDL, Clofibric Acid, Dose-Response Relationship, Drug, Fenofibrate, Humans, Lipoproteins, HDL, Receptors, Lipoprotein, Scavenger Receptors, Class B, Thiourea

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


Alternate JournalJ. Lipid Res.
PubMed ID17533223
Grant ListHL-48739 / HL / NHLBI NIH HHS / United States
HL-52212 / HL / NHLBI NIH HHS / United States
N01 CO-12400 / CO / NCI NIH HHS / United States