de Jong S C, van den Berg M, Rauwerda J A, Stehouwer C D
Institute for Cardiovascular Research, Vrije Universiteit, Amsterdam, The Netherlands.
Semin Thromb Hemost. 1998;24(4):381-5. doi: 10.1055/s-2007-996026.
Hyperhomocysteinemia is an independent risk factor for atherothrombotic disease. The mechanism by which homocysteine induces atherosclerosis and thrombosis is not fully understood. Data on arterial histology in humans with homocystinuria and mild hyperhomocysteinemia are limited. In vitro studies as well as studies in animals and humans indicate that hyperhomocysteinemia induces dysfunction of the vascular endothelium, with loss of endothelium-dependent vasodilation and endothelial antithrombotic properties, and proliferation of vascular smooth muscle cells, which are key processes in current models of atherogenesis and thrombosis. One of the hypotheses is that homocysteine can lead to cellular dysfunction through a mechanism involving oxidative damage but future studies in humans are needed to confirm this. Studies in hyperhomocysteinemic vascular patients have shown that endothelial antithrombotic properties appear to be more severely impaired than in similar patients with normohomocysteinemia. Furthermore, impaired endothelium-dependent vasodilation has been observed in clinically healthy hyperhomocysteinemic subjects in whom no abnormalities were found in endothelial antithrombotic properties. Future studies involving homocysteine-lowering treatment in hyperhomocysteinemic patients with vascular disease and in clinically healthy hyperhomocysteinemic subjects are necessary to investigate the mechanisms by which homocysteine causes atherothrombotic disorders in humans.
高同型半胱氨酸血症是动脉粥样硬化血栓形成性疾病的一个独立危险因素。同型半胱氨酸诱发动脉粥样硬化和血栓形成的机制尚未完全明确。关于同型胱氨酸尿症和轻度高同型半胱氨酸血症患者的动脉组织学数据有限。体外研究以及在动物和人类中的研究表明，高同型半胱氨酸血症会导致血管内皮功能障碍，使内皮依赖性血管舒张功能及内皮抗血栓特性丧失，还会导致血管平滑肌细胞增殖，而这些都是当前动脉粥样硬化和血栓形成模型中的关键过程。其中一个假说是同型半胱氨酸可通过涉及氧化损伤的机制导致细胞功能障碍，但还需要对人类进行进一步研究以证实这一点。对高同型半胱氨酸血症血管疾病患者的研究表明，与同型半胱氨酸水平正常的类似患者相比，其内皮抗血栓特性似乎受损更严重。此外，在临床健康的高同型半胱氨酸血症受试者中也观察到了内皮依赖性血管舒张功能受损，而这些受试者的内皮抗血栓特性并无异常。有必要对患有血管疾病的高同型半胱氨酸血症患者以及临床健康的高同型半胱氨酸血症受试者进行涉及降低同型半胱氨酸治疗的进一步研究，以探究同型半胱氨酸在人类中引发动脉粥样硬化血栓形成性疾病的机制。
