Hicks R C, Golledge J, Mir-Hasseine R, Powell J T
Cardiovascular & Pulmonary Research Division, Charing Cross & Westminster Medical School, London, UK.
Nature. 1996 Feb 29;379(6568):818-20. doi: 10.1038/379818a0.
Normal plasma fibrinogen concentrations are critical to haemostasis. Higher fibrinogen concentrations are associated with increasing risk of atherosclerotic disease and with graft stenosis and occlusion after saphenous vein bypass surgery. 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. We report here that fibrinopeptides had no vasoactive effects on saphenous vein rings; however, fibrinogen (0-2 microM) 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.
正常的血浆纤维蛋白原浓度对止血至关重要。较高的纤维蛋白原浓度与动脉粥样硬化疾病风险增加以及大隐静脉搭桥手术后的移植物狭窄和闭塞有关。静脉移植物狭窄的特征是内膜平滑肌细胞局部增殖，导致移植物狭窄，血栓形成闭塞风险增加。据报道，在兔动脉中，纤维蛋白肽B具有血管收缩和促有丝分裂特性。我们在此报告，纤维蛋白肽对大隐静脉环没有血管活性作用；然而，纤维蛋白原（0-2 microM）影响内皮依赖性舒张，在较高浓度时随后出现再收缩。纤维蛋白原介导的舒张被钾通道阻滞剂和抗ICAM-1抗体抑制。血管活性介质和促有丝分裂原合成的耦合信号通路可能是纤维蛋白原与静脉移植物病理发展之间关联的基础。
