Direct proinflammatory effect of C-reactive protein on human endothelial cells

Abstract

Background - The acute-phase reactant C-reactive protein (CRP) is an important risk factor for coronary heart disease. However, the possible effects of CRP on vascular cells are not known. Methods and Results - We tested the effects of CRP on expression of adhesion molecules in both human umbilical vein and coronary artery endothelial cells. Expression of vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM-1), and E-selectin was assessed by flow cytometry. InCubation with recombinant human CRP (10 μg/mL) for 24 hours induced an ≃10-fold increase in expression of ICAM-1 and a significant expression Of VCAM-1, whereas a 6-hour incubation induced significant E-selectin expression. Adhesion molecule induction was similar to that observed in endothelial cells activated with interleukin-1β. In coronary artery endothelial cells, induction of ICAM-1 and VCAM-1 was already present at 5 μg/mL and reached a maximum at 50 μg/mL, at which point a substantial increase in expression of E-selectin was also evident. The CRP effect was dependent on presence of human serum in the culture medium, because no effect was seen in cells cultured with serum-free medium. In contrast, interleukin-1β was able to induce adhesion molecule expression in the absence of human serum. Conclusions - CRP induces adhesion molecule expression in human endothelial cells in the presence of serum. These findings support the hypothesis that CRP may play a direct role in promoting the inflammatory component of atherosclerosis and present a potential target for the treatment of atherosclerosis.