McCully K S
Department of Veterans Affairs Medical Center, Providence, RI 02908.
Ann Clin Lab Sci. 1993 Nov-Dec;23(6):477-93.
The atherogenic properties of homocysteine were discovered by observation of arteriosclerosis in children with homocystinuria caused by inherited deficiency of three different enzymes. Hyperhomocysteinemia is generally recognized as an independent risk factor for coronary, cerebral, and peripheral atherosclerosis. Hyperhomocysteinemia is caused by heterozygosity for homocystinuria, micronutrient deficiency from dietary imbalance, toxins, drugs, hormones, and other factors, explaining many key observations concerning the epidemiology of atherosclerosis. The etiological factors for atherosclerosis are believed to increase conversion of methionine to homocysteine thiolactone, the reactive cyclic internal lactone of homocysteine. The free amino groups of low density lipoprotein (LDL) are thiolated by homocysteine thiolactone, causing aggregation and increased uptake of LDL by macrophages, explaining lipid deposition in atheromas. Homocysteine thiolactone, released from homocysteinylated LDL within vascular wall, promotes intimal injury, oxidation of cholesterol and unsaturated lipids, platelet aggregation, thrombogenic factors, myointimal hyperplasia, deposition of sulfated glycosaminoglycans, fibrosis and calcification of atherosclerotic plaques.
同型半胱氨酸的致动脉粥样硬化特性是通过观察由三种不同酶的遗传性缺乏导致同型胱氨酸尿症的儿童的动脉硬化发现的。高同型半胱氨酸血症通常被认为是冠状动脉、脑和外周动脉粥样硬化的独立危险因素。高同型半胱氨酸血症是由同型胱氨酸尿症的杂合性、饮食不均衡导致的微量营养素缺乏、毒素、药物、激素及其他因素引起的，这解释了许多关于动脉粥样硬化流行病学的关键观察结果。动脉粥样硬化的病因被认为会增加蛋氨酸向同型半胱氨酸硫内酯（同型半胱氨酸的反应性环状内酯）的转化。低密度脂蛋白（LDL）的游离氨基被同型半胱氨酸硫内酯硫醇化，导致巨噬细胞对LDL的聚集和摄取增加，这解释了动脉粥样瘤中的脂质沉积。从血管壁内的同型半胱氨酸化LDL释放的同型半胱氨酸硫内酯会促进内膜损伤、胆固醇和不饱和脂质的氧化、血小板聚集、血栓形成因子、肌内膜增生、硫酸化糖胺聚糖的沉积、动脉粥样硬化斑块的纤维化和钙化。
