C-Reactive Protein-Induced Expression of CD40-CD40L and the Effect of Lovastatin and Fenofibrate on It in Human Vascular Endothelial Cells(Pharmacology)

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概要

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• 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 μg/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 (5×10^<-5>, 10^<-4>, 2×10^<-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.

• 公益社団法人日本薬学会の論文
• 2004-10-01

著者

• Liu Juntian

  Department of Pharmacology, Xi’an Jiaotong University School of Medicine, P. R. China

• Liu J

  Department Of Pharmacology Xi'an Jiaotong University School Of Medical

• LIN Rong

  Department of Internal Medicine, Ho-Ping Branch, Taipei City Hospital

• Lin Rong

  Department Of Pharmacology Xi'an Jiaotong University School Of Medical:key Laboratory Of Enviro

• Lin Rong

  Department Of Cardiology First Hospital Of Quanzhou Affiliated To Fujian Medical University

• Liu Juntian

  Department Of Pharmacology Xi'an Jiaotong University School Of Medical

• GAN Weijie

  Department of Pharmacology, Xi'an Jiaotong University School of Medical

• YANG Guangde

  College of Pharmacy Xi'an Jiaotong University

• Gan Weijie

  Department Of Pharmacology Xi'an Jiaotong University School Of Medical

• Yang Guangde

  Department Of Pharmacy Xi'an Jiaotong University School Of Medical

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