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

Article

关键词: HIGH-DENSITY-LIPOPROTEIN;    MONOCYTE-DERIVED MACROPHAGES;    CELLULAR CHOLESTEROL EFFLUX;    B TYPE-I;    SCAVENGER RECEPTOR;    SR-BI;    PPAR-GAMMA;    ALPHA;    CELLS;    CLONING;   

DOI  :  10.1161/01.CIR.101.20.2411

来源: SCIE

【 摘 要 】

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 alpha and PPAR gamma staining. Activation of PPAR alpha and PPAR gamma 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 gamma or PPAR alpha 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.

【 授权许可】

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