(Circulation. 2000;101:2411.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
CLA-1/SR-BI Is Expressed in Atherosclerotic Lesion Macrophages and Regulated by Activators of Peroxisome Proliferator-Activated Receptors
From the U.325 INSERM, Département d’Athérosclerose, Institut Pasteur de Lille, and the Faculté de Pharmacie, Université de Lille II (G.C., F.G.G., P.P., J.-C.F., J.N.-F., B.S.), and U.321 INSERM, Hôpital de la Pitié (S.G., M.A., J.C.), and U.141 INSERM, Hôpital Lariboisière (Z.M., A.T.), Paris, France. The first 2 authors contributed equally to this work.
Correspondence to Bart Staels, U.325 INSERM, Institut Pasteur de Lille, 1, rue Calmette BP245, 59019 Lille, France. E-mail bart.staels{at}pasteur-lille.fr
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 PPAR
and
PPAR
staining. Activation of PPAR and PPAR 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 PPAR or PPAR 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.
Key Words: receptors • atherosclerosis • plaque • lipoproteins • immunohistochemistry
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