Wilcken D E, Dudman N P
Department of Cardiovascular Medicine, University of New South Wales, Sydney, Australia.
Haemostasis. 1989;19 Suppl 1:14-23. doi: 10.1159/000216091.
Thrombogenesis and accelerated atherogenesis occur in the homocystinurias, both those due to recessively inherited cystathionine beta-synthase deficiency and to disorders of remethylation of homocysteine to methionine. The evidence strongly implicates high levels of plasma homocysteine as the mediator. Homocysteine damages cultured human venous and arterial endothelial cells and enhances detachment from their substrate, changes not found with comparable concentrations of other amino acids tested. Homocysteine is oxidized in vitro to homocystine in an oxygen-dependent reaction producing hydrogen peroxide. Since the effects of homocysteine in cell cultures can be prevented by catalase, hydrogen-peroxide-induced injury may be the mechanism responsible. Five different laboratories have documented an association between mild homocysteinaemia and premature vascular disease. The majority of affected patients are heterozygotes for cystathionine beta-synthase deficiency whose endothelial cells may have an enhanced susceptibility to injury by homocysteine. Mild homocysteinaemia also occurs in chronic renal failure in which vascular disease is prominent. Mechanisms linking mild homocysteinaemia and possible vascular effects are not yet understood, but could involve prostaglandins and oxidized low-density lipoprotein, and possibly also free radicals.
在同型胱氨酸尿症中会发生血栓形成和动脉粥样硬化加速，这两种情况分别是由于隐性遗传的胱硫醚β-合酶缺乏以及同型半胱氨酸再甲基化为甲硫氨酸的紊乱所致。有充分证据表明，高水平的血浆同型半胱氨酸是介导因素。同型半胱氨酸会损害培养的人静脉和动脉内皮细胞，并增强其与底物的脱离，而在测试的其他氨基酸的可比浓度下未发现这种变化。同型半胱氨酸在体外通过产生过氧化氢的氧依赖性反应被氧化为同型胱氨酸。由于过氧化氢酶可预防同型半胱氨酸在细胞培养中的作用，因此过氧化氢诱导的损伤可能是其作用机制。五个不同的实验室已证明轻度高同型半胱氨酸血症与早发性血管疾病之间存在关联。大多数受影响的患者是胱硫醚β-合酶缺乏的杂合子，其内皮细胞可能对同型半胱氨酸损伤的易感性增强。轻度高同型半胱氨酸血症也发生在以血管疾病为突出表现的慢性肾衰竭中。轻度高同型半胱氨酸血症与可能的血管效应之间的联系机制尚不清楚，但可能涉及前列腺素和氧化型低密度脂蛋白，也可能涉及自由基。
