de Jong S C, Stehouwer C D, van den Berg M, Vischer U M, Rauwerda J A, Emeis J J
Institute for Cardiovascular Research, Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands.
Thromb Haemost. 1997 Nov;78(5):1332-7.
Hyperhomocysteinemia is associated with severe, premature atherosclerosis and thromboembolism. The mechanisms involved in the atherogenic and thrombotic complications of hyperhomocysteinemia are not understood. It has been suggested that hyperhomocysteinemia predisposes to atherosclerosis by injuring the vascular endothelium. Whether hyperhomocysteinemia is independently associated with changed endothelial function, either in the absence or the presence of clinically manifest atherosclerotic disease, is, however, not known. Therefore we investigated, both in patients with peripheral arterial occlusive disease and in healthy individuals, whether plasma protein markers of endothelial function differed between subjects with, and subjects without hyperhomocysteinemia. We studied 80 individuals under the age of 56 years: healthy individuals with (n = 20) and without (n = 20) hyperhomocysteinemia and patients with peripheral arterial occlusive disease with (n = 20) and without (n = 20) hyperhomocysteinemia. The following endothelium-derived proteins were measured as markers of endothelial cell function: von Willebrand factor (vWf) and von Willebrand factor propeptide (vWf: AgII), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), cellular fibronectin (cFN) and thrombomodulin (TM). In addition we assessed C-reactive protein (CRP). vWf, vWf: AgII, tPA and CRP were significantly higher in the patients with peripheral arterial occlusive disease than in the healthy individuals. No differences in marker protein plasma levels were found between individuals with, and those without hyperhomocysteinemia, apart from vWf, which was significantly raised in hyperhomocysteinemic as compared to normohomocysteinemic patients. We did not find any evidence for an independent association between hyperhomocysteinemia and protein markers of endothelial cell function in healthy subjects.
高同型半胱氨酸血症与严重的早发性动脉粥样硬化和血栓栓塞有关。高同型半胱氨酸血症的致动脉粥样硬化和血栓形成并发症所涉及的机制尚不清楚。有人提出，高同型半胱氨酸血症通过损伤血管内皮而易患动脉粥样硬化。然而，无论是否存在临床明显的动脉粥样硬化疾病，高同型半胱氨酸血症是否与内皮功能改变独立相关尚不清楚。因此，我们在患有外周动脉闭塞性疾病的患者和健康个体中，研究了有高同型半胱氨酸血症和无高同型半胱氨酸血症的受试者之间内皮功能的血浆蛋白标志物是否存在差异。我们研究了80名年龄在56岁以下的个体：有高同型半胱氨酸血症（n = 20）和无高同型半胱氨酸血症（n = 20）的健康个体，以及有高同型半胱氨酸血症（n = 20）和无高同型半胱氨酸血症（n = 20）的外周动脉闭塞性疾病患者。测量了以下内皮衍生蛋白作为内皮细胞功能的标志物：血管性血友病因子（vWf）和血管性血友病因子前肽（vWf: AgII）、组织型纤溶酶原激活剂（tPA）、纤溶酶原激活剂抑制剂-1（PAI-1）、细胞纤连蛋白（cFN）和血栓调节蛋白（TM）。此外，我们评估了C反应蛋白（CRP）。外周动脉闭塞性疾病患者的vWf、vWf: AgII、tPA和CRP显著高于健康个体。除vWf外，有高同型半胱氨酸血症和无高同型半胱氨酸血症的个体之间标志物蛋白血浆水平未发现差异，与正常同型半胱氨酸血症患者相比，高同型半胱氨酸血症患者的vWf显著升高。我们没有发现任何证据表明健康受试者中高同型半胱氨酸血症与内皮细胞功能的蛋白标志物之间存在独立关联。
