Fibrinogen up-regulates the expression of monocyte chemoattractant protein1 in human saphenous vein endothelial cells

High concentrations of fibrinogen in plasma have been associated with an in creased risk of saphenous vein graft pathology. We have investigated the ab ility of fibrinogen to up-regulate the expression of monocyte chemoattracta nt protein 1 (MCP-1) in cultured human saphenous vein endothelial cells (HS VEC) isolated from saphenous vein. Increasing concentrations of fibrinogen (0-4 mu M) stimulated a 20-fold increase in MCP-1 secretion within 4 h, Inc ubation of HSVEC with 2 mu M fibrinogen for 4 h also caused a 2-fold increa se in the MCP-1-to-glyceraldehyde-3-phosphate dehydrogenase mRNA ratio. The fibrinogen-mediated MCP-1 secretion fell to basal levels after preincubati on of HSVEC with the complex of fibrinogen fragments D and E but remained u nchanged after preincubation of HSVEC with either fibrinogen fragment E, s- ICAM-1 or the pentapeptide GRGDV. In contrast, fibrinogen fragment D acted as a potent inhibitor of fibrinogen-mediated MCP-1 secretion. Labelled fibr inogen fragment D bound to HSVEC with a K-d of 6.5 mu M. These findings ind icate that fibrinogen, at physiological concentrations, uses an epitope on the fibrinogen D domain to bind to a receptor on HSVEC to up-regulate MCP-1 expression and secretion. This receptor seems to be distinct from intercel lular adhesion molecule 1 and the integrins previously recognized as fibrin ogen receptors.