Dayal Sanjana, Lentz Steven R
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa.
Antioxid Redox Signal. 2007 Nov;9(11):1899-909. doi: 10.1089/ars.2007.1806.
Hyperhomocysteinemia is a risk factor for cardiovascular disease, stroke, and thrombosis. Several animal models of hyperhomocysteinemia have been developed by using both dietary and genetic approaches. These animal models have provided considerable insight into the mechanisms underlying the adverse vascular effects of hyperhomocysteinemia. Accumulating evidence suggests a significant role of altered cellular redox reactions in the vascular phenotype of hyperhomocysteinemia. Redox effects of hyperhomocysteinemia are particularly important in mediating the adverse effects of hyperhomocysteinemia on the endothelium, leading to loss of endothelium-derived nitric oxide and vasomotor dysfunction. Redox reactions also may be key factors in the development of vascular hypertrophy, thrombosis, and atherosclerosis in hyperhomocysteinemic animals. In this review, we summarize the metabolic relations between homocysteine and the cellular redox state, the vascular phenotypes that have been observed in hyperhomocysteinemic animals, the evidence for altered redox reactions in vascular tissue, and the specific redox reactions that may mediate the vascular effects of hyperhomocysteinemia.
高同型半胱氨酸血症是心血管疾病、中风和血栓形成的一个危险因素。通过饮食和基因方法已经建立了几种高同型半胱氨酸血症的动物模型。这些动物模型为深入了解高同型半胱氨酸血症不良血管效应的潜在机制提供了大量信息。越来越多的证据表明，细胞氧化还原反应的改变在高同型半胱氨酸血症的血管表型中起重要作用。高同型半胱氨酸血症的氧化还原效应在介导其对内皮的不良影响方面尤为重要，导致内皮源性一氧化氮丧失和血管舒缩功能障碍。氧化还原反应也可能是高同型半胱氨酸血症动物血管肥大、血栓形成和动脉粥样硬化发展的关键因素。在本综述中，我们总结了同型半胱氨酸与细胞氧化还原状态之间的代谢关系、在高同型半胱氨酸血症动物中观察到的血管表型、血管组织中氧化还原反应改变的证据以及可能介导高同型半胱氨酸血症血管效应的特定氧化还原反应。
