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Biol Pharm Bull. 2004 Oct;27(10):1537-43.

C-reactive protein-induced expression of CD40-CD40L and the effect of lovastatin and fenofibrate on it in human vascular endothelial cells.

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1
Department of Pharmacology, Medical School of Xi'an Jiaotong University, PR China. linrong@mail.xjtu.edu.cn

Abstract

Inflammation plays a pivotal role in the formation of atherosclerosis. In addition to being a risk marker for cardiovascular diseases, the role of C-reactive protein (CRP) in atherogenesis has been supported by more recent data. CD40-CD40L system is proven to be an important mediator of several auto-immune and chronic inflammation diseases. Interruption of CD40-CD40L signaling pathway not only reduces the initiation and progression of atherosclerotic lesions, but also modulates plaque architecture. By using a flow cytometry and western blotting, we found that incubation of human umbilical vein endothelial cells (HUVECs) with CRP resulted in a time- and dose-dependent increase in the cell-surface expression of CD40 and CD40L. In addition, CRP (25 microg/ml) increased gelatinolytic activities of MMP-2 and MMP-9. Anti-CD40 antibody significantly reversed the upregulated activities of MMP-2 and MMP-9 induced by CRP with gelatin zymography. Furthermore, lovastatin (10(-7), 10(-6), 10(-5) mol/l) and fenofibrate (5 x 10(-5), 10(-4), 2 x 10(-4) mol/l) significantly diminished the expression of CD40, CD40L and gelatinase activities (MMP-2, MMP-9) induced by CRP in HUVECs. In conclusion, our data provide evidence to support the direct pro-inflammatory effects of CRP via CD40-CD40L signaling pathway involved in the pathogenesis of atherosclerosis, and lovastatin and fenofibrate possess anti-inflammatory effects independent of their lipid-lowering action.

PMID:
15467191
[Indexed for MEDLINE]
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