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

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

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

Thomas J F Nieland,Jared T Shaw,Firoz A Jaipuri,Zoltan Maliga,Jay L Duffner,Angela N Koehler,Monty Krieger,

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.

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

TJ Nieland,JT Shaw,FA Jaipuri,Z Maliga,JL Duffner,AN Koehler,M Krieger,

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

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of lipid research

VOLUME: 48

Page Numbers: 1832-45

Journal Abbreviation: J. Lipid Res.

ISSN: 0022-2275

DAY: 28

MONTH: 05

YEAR: 2007

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

Number of References:

LANGUAGE: eng

NlmUniqueID: 376606

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

KEYWORDS: Thiourea

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Influence of HDL-cholesterol-elevating drugs on the in vitro activity of the HDL receptor SR-BI. Information

Substance Name: Clofibric Acid

Registry Number: 882-09-7

Grant and Affiliation Information for Influence of HDL-cholesterol-elevating drugs on the in vitro activity of the HDL receptor SR-BI.

AFFILIATION: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Country: United States

AGENCY: United States NCI

GRANT: N01 CO-12400

ACRONYM: CO

MEDLINETA: J Lipid Res

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