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Overexpression of the HDL receptor SR-BI alters plasma HDL and bile cholesterol levels

Nature volume 387, pages 414417 (22 May 1997) | Download Citation

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Abstract

The risk of atherosclerosis, a leading cause of cardiovascular disease and death, is inversely related to plasma levels of high-density lipoprotein (HDL) cholesterol, although the mechanism of this protective effect is unclear1. The class B scavenger receptor, SR-BI, is the first HDL receptor to be well defined at a molecular level and is a mediator of selective cholesterol uptake in vitro 2. It is expressed most abundantly in steroidogenic tissues, where it is coordinately regulated with steroidogenesis by adrenocorticotropic hormone (ACTH), human chorionic gonadotropin (hCG) and oestrogen, and in the liver, where its expression in rats is suppressed by oestrogen3,4. Here we show that adenovirus-mediated, hepatic overexpression of SR-BI in mice on both sinusoidal and canalicular surfaces of hepatocytes results in the virtual disappearance of plasma HDL and a substantial increase in biliary cholesterol. SR-BI may directly mediate these effects by increasing hepatic HDL cholesterol uptake or by increasing cholesterol secretion into bile, or both. These results indicate that SR-BI may be important in hepatic HDL metabolism, in determining plasma HDL concentrations, and in controlling cholesterol concentrations in bile, and thus may influence the development and progression of atherosclerosis and gallstone disease.

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Affiliations

  1. Institute for Human Gene Therapy and Department of Molecular and Cellular Engineering, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA

    • Karen F. Kozarsky
    •  & Mary H. Donahee
  2. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    • Attilio Rigotti
    •  & Monty Krieger
  3. Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA

    • Elazer R. Edelman
  4. Harvard-Massachusetts Institute of Technology, Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA

    • Sohah N. Iqbal
    •  & Elazer R. Edelman

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https://doi.org/10.1038/387414a0

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