Effects of C-reactive protein on the release of von Willebrand factor, E-selectin, thrombomodulin and intercellular adhesion molecule-1 from human umbilical vein endothelial cells

Increased levels of various plasma molecules, including C-reactive protein (CRP), and endothelial markers von Willebrand factor (vWF), E-selectin, intercellular adhesion molecule-1 (ICAM-1) and thrombomodulin all predict the development and/or progression of cardiovascular disease. As CRP has been shown to upregulate the expression of adhesion molecules on the surface of human umbilical vein endothelial cells (HUVECs) in vitro, we hypothesized that CRP would induce the release of increased levels of the endothelial markers from HUVECs. Accordingly, recombinant human CRP was added to the culture medium of confluent monolayers of HUVECs at physiological to pathological doses of 1-50 mug/ml for 3-48 h. Markers were measured in supernatants by commercial enzyme-linked immunosorbent assays. We found that increased release of thrombomodulin was induced by 20 and 50 mug/ml CRP after 48 h. Increased ICAM-1 was induced by 50 mug/ml CRP after 24 and 48 h. There was no clear influence of CRP on E-selectin, but 20 and 50 mug/ml CRP inhibited the release of vWF. Our data provide further evidence of a link between increased levels of ICAM-1, thrombomodulin and CRP in atherosclerosis, but they counter reports of a direct, possibly causal, relationship between CRP and increases in E-selectin or vWF. (C) 2003 Lippincott Williams Wilkins.