Impaired EDRF production by endothelial cells exposed to fibrin monomer and FDP.

Impaired EDRF production by endothelial cells exposed to fibrin monomer and FDP.
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暴露于纤维蛋白单体和 FDP 的内皮细胞产生的 EDRF 受损。

DOI:
10.1152/ajpcell.1995.268.2.c520
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发表时间:
1995
期刊:
The American journal of physiology.
影响因子:
--
通讯作者:
Loscalzo,J
Loscalzo,J
中科院分区:
--
文献类型:
--
作者:
Freedman,JE;Fabian,A;Loscalzo,J

文献摘要

被引文献

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动脉粥样斑块内发现的纤维蛋白和纤维蛋白原及其蛋白水解降解产物可能会导致血管功能障碍。我们监测了牛主动脉内皮细胞 (BAEC) 在暴露于纤维蛋白原、纤维蛋白单体 (FM) 以及纤维蛋白和纤维蛋白原降解产物 (FDP) 后产生的内皮源性舒张因子 (EDRF)。与用纤维蛋白原孵育的细胞相比,用 FM 和 FDP 孵育的细胞抑制血小板聚集的能力较差,并且这种效应与浓度依赖性的 EDRF 产生减少相关:使用光解化学发光系统测定,与 FM 或 FDP 而不是纤维蛋白原孵育的 BAEC 产生的一氧化氮 (NO) 显着减少。将 BAEC 与纤维蛋白原、FM 或 FDP 一起孵育并探测组成型牛内皮 NO 合酶 mRNA,Northern 分析表明暴露于 FDP 或 FM 的细胞中表达降低。这些数据表明 FM 和 FDP 减少 BAEC 产生的 EDRF 并减弱组成型 NO 合酶表达。这些作用可能代表了血栓形成决定因素对内皮功能产生不利影响的机制,从而可能损害血管舒缩反应并促进动脉粥样硬化血栓形成。
Fibrin and fibrinogen and their proteolytic degradation products, found within the atheroma, may contribute to vascular dysfunction. We monitored the production of endothelium-derived relaxing factor (EDRF) by bovine aortic endothelial cells (BAEC) after exposure to fibrinogen, fibrin monomer (FM), and fibrin and fibrinogen degradation products (FDP). Cells incubated with FM and FDP, compared with cells incubated with fibrinogen, were less able to inhibit platelet aggregation, and this effect correlated with a concentration-dependent decrease in EDRF production: BAEC incubated with FM or FDP, but not fibrinogen, produced significantly less nitric oxide (NO), as determined using a photolysis-chemiluminescence system. Northern analysis of BAEC incubated with fibrinogen, FM, or FDP and probed for constitutive bovine endothelial NO synthase mRNA demonstrated decreased expression in cells exposed to FDP or FM. These data show that FM and FDP reduce EDRF produced by BAEC and attenuate constitutive NO synthase expression. These effects may represent a mechanism by which thrombotic determinants adversely affect endothelial function and thereby potentially impair vasomotor responses and contribute to atherothrombogenesis.