CLA-1/SR-BI is expressed in atherosclerotic lesion macrophages and regulated by activators of peroxisome proliferator-activated receptors

  • Circulation. 2000 May 23;101(20):2411-7. doi: 10.1161/01.cir.101.20.2411.
G Chinetti  1 ,  F G Gbaguidi ,  S Griglio ,  Z Mallat ,  M Antonucci ,  P Poulain ,  J Chapman ,  J C Fruchart ,  A Tedgui ,  J Najib-Fruchart ,  B Staels
Affiliations
  • 1. U.325 INSERM, Département d'Athérosclerose, Institut Pasteur de Lille, France.
PMID: 10821819 DOI: 10.1161/01.cir.101.20.2411
Abstract

Background: The scavenger receptors are cell-surface receptors for native and modified lipoproteins that play a critical role in the accumulation of Lipids by Macrophages. CLA-1/SR-BI binds HDL with high affinity and is involved in the Cholesterol reverse-transport pathway. Peroxisome proliferator-activated receptors (PPARs) are Transcription Factors regulating the expression of genes implicated in Lipid Metabolism, cellular differentiation, and inflammation. Here, we investigated the expression of CLA-1/SR-BI in Macrophages and its regulation by PPARs.

Methods and results: CLA-1 is undetectable in human monocytes and is induced upon differentiation into Macrophages. Immunohistological analysis on human atherosclerotic lesions showed high expression of CLA-1 in Macrophages of the lipid core colocalizing with PPARalpha and PPARgamma staining. Activation of PPARalpha and PPARgamma resulted in the induction of CLA-1 protein expression in monocytes and in differentiated Macrophages. Finally, SR-BI expression is increased in atherosclerotic lesions of apoE-null mice treated with either PPARgamma or PPARalpha ligands.

Conclusions: Our data demonstrate that CLA-1/SR-BI is expressed in atherosclerotic lesion Macrophages and induced by PPAR activation, identifying a potential role for PPARs in Cholesterol homeostasis in atherosclerotic lesion Macrophages.

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