期刊
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
卷 25, 期 6, 页码 1220-1224出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.ATV.0000159163.52632.1b
关键词
atherosclerosis; foam cell; macrophage; toll-like receptor; aP2
资金
- NIAMS NIH HHS [AR 39639] Funding Source: Medline
Objective - Toll- like receptors ( TLRs) recognize pathogens and mediate signaling pathways important for host defense. Recent studies implicate TLR polymorphisms in atherosclerosis risk in humans. Adipocyte fatty acid - binding protein ( aP2) is present in macrophages and has an important role in atherosclerotic plaque development. We investigated aP2 expression in RAW 264.7 cells treated with lipopolysaccharide ( LPS) and other TLR agonists and assessed lipid accumulation in these activated murine macrophages. Methods and Results - Stimulation with LPS, a TLR4 ligand, resulted in a 56- fold increase in aP2 mRNA expression, and zymosan, a TLR2 ligand, induced an approximate to 1500- fold increase. Polyinosine: polycytidylic acid ( poly I: C), a TLR3 ligand, led to a 9- fold increase. Levels of aP2 protein were significantly increased in LPS or zymosan- treated macrophages compared with control or poly I: C - treated cells. In addition, the cholesteryl ester content of LPS or zymosan- treated macrophages was approximate to 5- fold greater in the presence of low- density lipoprotein, and triglyceride content was approximate to 2- fold greater in the absence of exogenous lipid than control or poly I: C - treated cells. Conclusions - Expression of macrophage aP2 is induced on TLR activation and parallels increases in cholesteryl ester and triglyceride levels. These results provide a molecular link between the known roles of TLR and aP2 in foam cell formation.
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