Overexpression of SR-BI by Adenoviral Vector Reverses the Fibrate-induced Hypercholesterolemia of Apolipoprotein E-deficient Mice

Tao Fu, Karen F. Kozarsky, Jayme Borensztajn*

*Corresponding author for this work

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

The hypercholesterolemia characteristic of apolipoprotein (apoE)-deficient mice fed on a regular chow diet is caused by the abnormal accumulation of apoB-48-carrying remnants of chylomicrons and very low density lipoproteins in the plasma. Treatment of apoE-deficient mice with ciprofibrate or other peroxisome proliferator-activated receptor α agonists severely aggravates their hypercholesterolemia by interfering with one or more mechanisms of remnant removal from the circulation that do not require mediation by apoE (Fu, T., Kashireddy, P., and Borensztajn, J. (2003) Biochem. J. 373, 941-947). In the present investigation we report that ciprofibrate treatment causes the down-regulation of hepatic scavenger receptor class B, type I (SR-BI) protein expression in the livers of apoE-deficient mice. On cessation of the treatment SR-BI expression returns to its pretreatment levels, coinciding with a reversal of the hypercholesterolemia to base-line concentrations. Restoration of SR-BI expression in ciprofibrate-treated apoE-defieient mice by recombinant adenoviral gene transfer abolishes the ciprofibrate-induced over accumulation of apoB-48-carrying remnants in the plasma. We also report that remnants isolated from the plasma of ciprofibrate-treated apoE-deficient mice bind to murine SR-BI expressed in stably transfected cultured cells. These observations suggest that, in addition to its well established role as high density lipoprotein receptor, SR-BI can also function as a remnant receptor responsible for the clearance of remnants from the circulation of apoE-deficient mice.

Original languageEnglish (US)
Pages (from-to)52559-52563
Number of pages5
JournalJournal of Biological Chemistry
Volume278
Issue number52
DOIs
StatePublished - Dec 26 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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