Vasoactive effects of fibrinogen on saphenous vein

Normal plasma fibrinogen concentrations are critical to haemostasis. Higher fibrinogen concentrations are associated with increasing risk of atherosclerotic disease(1) and with graft stenosis and occlusion after saphenous vein bypass surgery(2,3). Vein graft stenosis is characterized by the localized proliferation of intimal smooth muscle cells, causing narrowing of the graft with increased risk of thrombotic occlusion. In rabbit arteries, fibrinopeptide B is reported to have both vasoconstrictor and mitogenic properties(4,5). We report here that fibrinopeptides had no vasoactive effects on saphenous vein rings; however, fibrinogen (0-2 mu M) affected an endothelium-dependent relaxation, followed by recontraction at higher concentrations. The fibrinogen-mediated relaxation was inhibited by K+-channel blockers and antibodies to ICAM-1. Coupled signalling pathways for the synthesis of vasoactive mediators and mitogens could underlie the association between fibrinogen and the development of vein graft pathology.