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

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

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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 (IC50 ∼ 1 μM), 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 a, 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.

Original languageEnglish (US)
Pages (from-to)1832-1845
Number of pages14
JournalJournal of Lipid Research
Volume48
Issue number8
DOIs
StatePublished - Aug 2007
Externally publishedYes

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CD36 Antigens
HDL Cholesterol
Pharmaceutical Preparations
Fenofibrate
Fibric Acids
Niacin
Plasmas
In Vitro Techniques
high density lipoprotein receptors
Bezafibrate
Gemfibrozil
MHC Class I Genes
Clofibrate
Gene Knockout Techniques
Peroxisome Proliferator-Activated Receptors
Prodrugs
Structure-Activity Relationship
Particle Size
Metabolism
Liposomes

Keywords

  • Fenofibrate
  • Fibrates
  • HDL376
  • High density lipoprotein
  • Lipoprotein metabolism
  • Niacin
  • Scavenger receptor class B type I
  • Structure-activity relationship

ASJC Scopus subject areas

  • Endocrinology

Cite this

Nieland, T. J. F., Shaw, J. T., Jaipuri, F. A., Maliga, Z., Duffner, J. L., Koehler, A. N., & Krieger, M. (2007). Influence of HDL-cholesterol-elevating drugs on the in vitro activity of the HDL receptor SR-BI. Journal of Lipid Research, 48(8), 1832-1845. https://doi.org/10.1194/jlr.M700209-JLR200

Influence of HDL-cholesterol-elevating drugs on the in vitro activity of the HDL receptor SR-BI. / Nieland, Thomas J F; Shaw, Jared T.; Jaipuri, Firoz A.; Maliga, Zoltan; Duffner, Jay L.; Koehler, Angela N.; Krieger, Monty.

In: Journal of Lipid Research, Vol. 48, No. 8, 08.2007, p. 1832-1845.

Research output: Contribution to journalArticle

Nieland, TJF, Shaw, JT, Jaipuri, FA, Maliga, Z, Duffner, JL, Koehler, AN & Krieger, M 2007, 'Influence of HDL-cholesterol-elevating drugs on the in vitro activity of the HDL receptor SR-BI', Journal of Lipid Research, vol. 48, no. 8, pp. 1832-1845. https://doi.org/10.1194/jlr.M700209-JLR200
Nieland, Thomas J F ; Shaw, Jared T. ; Jaipuri, Firoz A. ; Maliga, Zoltan ; Duffner, Jay L. ; Koehler, Angela N. ; Krieger, Monty. / Influence of HDL-cholesterol-elevating drugs on the in vitro activity of the HDL receptor SR-BI. In: Journal of Lipid Research. 2007 ; Vol. 48, No. 8. pp. 1832-1845.
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