2004 Volume 27 Issue 10 Pages 1537-1543
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.