High concentrations of fibrinogen in plasma have been associated with an increased risk of saphenous vein graft pathology. We have investigated the ability of fibrinogen to up-regulate the expression of monocyte chemoattractant protein 1 (MCP-1) in cultured human saphenous vein endothelial cells (HSVEC) isolated from saphenous vein. Increasing concentrations of fibrinogen (0-4 μM) stimulated a 20-fold increase in MCP-1 secretion within 4 h. Incubation of HSVEC with 2 μM fibrinogen for 4 h also caused a 2-fold increase in the MCP-1-to-glyceraldehyde-3-phosphate dehydrogenase mRNA ratio. The fibrinogen-mediated MCP-1 secretion fell to basal levels after preincubation of HSVEC with the complex of fibrinogen fragments D and E but remained unchanged 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 fibrinogen fragment D bound to HSVEC with a Kd of 6.5 μM. These findings indicate 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 intercellular adhesion molecule 1 and the integrins previously recognized as fibrinogen receptors.
Fibrinogen up-regulates the expression of monocyte chemoattractant protein 1 in human saphenous vein endothelial cells
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Suzanne L. HARLEY, Janet T. POWELL; Fibrinogen up-regulates the expression of monocyte chemoattractant protein 1 in human saphenous vein endothelial cells. Biochem J 1 August 1999; 341 (3): 739–744. doi: https://doi.org/10.1042/bj3410739
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