Haynes William G
Divisions of Cardiovascular Diseases and Clinical Pharmacology, Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242-1081, USA.
Cardiovasc Drugs Ther. 2002 Sep;16(5):391-9. doi: 10.1023/a:1022130217463.
Homocysteine is a metabolic product of methyl group donation by the amino acid methionine. Moderate elevation of plasma homocysteine (>15 microM) is most commonly caused by B-vitamin deficiencies, especially folic acid, B(6) and B(12). Genetic factors, certain drugs and renal impairment may also contribute. Homocysteine has several potentially deleterious vascular actions. These include increased oxidant stress, impaired endothelial function, stimulation of mitogenesis, and induction of thrombosis. Homocysteine also appears to increase arterial pressure. In humans, experimental induction of hyperhomocysteinemia by methionine loading rapidly causes profound impairment of endothelium-dependent dilatation in both resistance and conduit arteries. This endothelial dysfunction can be reversed by administration of antioxidants. Epidemiological evidence suggests that homocysteine acts as an independent risk factor for atherosclerosis, thrombosis and hypertension. Prospective studies have shown that elevated plasma homocysteine concentrations in the top quintile of the population (>12 microM) increase risk of cardiovascular disease by about 2-fold. There are currently no data available from randomized, controlled trials of the effects of lowering plasma homocysteine on atherothrombotic events. Nonetheless, it would seem appropriate to screen for and treat hyperhomocysteinemia in individuals with progressive or unexplained atherosclerosis. Folic acid and vitamins B(6) and B(12) are the mainstay of therapy. Treatment of moderately elevated plasma homocysteine in patients without atherosclerosis should be deferred until the completion of randomized outcome trials.
同型半胱氨酸是氨基酸甲硫氨酸进行甲基供体作用后的代谢产物。血浆同型半胱氨酸中度升高（>15微摩尔/升）最常见的原因是B族维生素缺乏，尤其是叶酸、维生素B6和维生素B12。遗传因素、某些药物和肾功能损害也可能起作用。同型半胱氨酸具有几种潜在的有害血管作用。这些作用包括增加氧化应激、损害内皮功能、刺激有丝分裂以及诱导血栓形成。同型半胱氨酸似乎还会升高动脉血压。在人类中，通过甲硫氨酸负荷实验性诱导高同型半胱氨酸血症会迅速导致阻力动脉和输送动脉的内皮依赖性舒张功能严重受损。这种内皮功能障碍可通过给予抗氧化剂得到逆转。流行病学证据表明，同型半胱氨酸是动脉粥样硬化、血栓形成和高血压的独立危险因素。前瞻性研究表明，人群中处于最高五分位数（>12微摩尔/升）的血浆同型半胱氨酸浓度升高会使心血管疾病风险增加约2倍。目前尚无关于降低血浆同型半胱氨酸对动脉粥样硬化血栓形成事件影响的随机对照试验数据。尽管如此，对于患有进行性或不明原因动脉粥样硬化的个体，筛查和治疗高同型半胱氨酸血症似乎是合适的。叶酸以及维生素B6和维生素B12是治疗的主要手段。对于无动脉粥样硬化患者的血浆同型半胱氨酸中度升高的治疗应推迟到随机结局试验完成之后。
