Modulation of C-Reactive Protein–Mediated Monocyte Chemoattractant Protein-1 Induction in Human Endothelial Cells by Anti-Atherosclerosis Drugs

Abstract

Background—C-reactive protein (CRP) induces adhesion molecule expression by endothelial cells. However, the effects of CRP on chemokine expression by endothelial cells are not known. Methods and Results—We tested the effects of CRP on the production of the chemokines monocyte chemoattractant protein-1 (MCP-1) and RANTES in cultured human umbilical vein endothelial cells. The secretion of chemokines was assessed by ELISA. Incubation with 100 μg/mL recombinant human CRP induced a 7-fold increase in MCP-1 but no change in RANTES secretion. We showed that the effect of CRP on MCP-1 was present even at 5 μg/mL CRP, with stepwise increases as the CRP concentration was increased to 10, 50, and 100 μg/mL. The effect of CRP on MCP-1 induction was not influenced by aspirin (at concentrations up to 1 mmol/L), but it was significantly inhibited by 5 μmol/L simvastatin. The peroxisome proliferator-activated receptor-α activators fenofibrate (100 μmol/L) and Wy-14649 (100 μmol/L) almost completely abolished the induction of MCP-1, but the peroxisome proliferator-activated receptor-γ activator ciglitazone had only a moderate effect. Conclusions—These results further strengthen the role of CRP in the pathogenesis of vascular inflammation and, likely, atherosclerosis and provide a crucial insight into a novel mechanism of action of anti-atherosclerosis drugs such as simvastatin and fenofibrate.