Jean Mayer Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts.
Nutrition and Brain Health Laboratory, The Institute of Biochemistry Food and Nutrition Science, The Robert H. Smith Faculty of Agriculture Food and the Environment, The Hebrew University of Jerusalem, Israel.
Ann N Y Acad Sci. 2016 Jan;1363:18-25. doi: 10.1111/nyas.12962. Epub 2015 Dec 8.
The homocysteine theory of arteriosclerosis received credence when it was shown that after a methionine load, circulating homocysteine-cysteine concentrations were higher in cardiovascular disease patients than in healthy controls. Subsequent studies showing associations between homocysteine and coronary artery disease, stroke and cognitive impairment, relied on small increases in homocysteine concentration unlike the very high homocysteine seen in the rare genetic disorders that lead to homocystinuria and much higher homocysteine levels. Subsequent studies in cell culture, animals, and humans showed that a variety of cardiovascular adverse effects of "high homocysteine" introduced either as a nonphysiological bolus or as a methionine load led to high homocysteine. We fed apolipoprotein E-deficient mice diets designed to achieve three conditions: (1) high methionine intake with normal blood homocysteine, (2) high methionine intake with B vitamin deficiency and hyperhomocysteinemia, and (3) normal methionine intake with both B vitamin deficiency and hyperhomocysteinemia. We found that the mice fed methionine-rich diets had significant atheromatous pathology in the aortic arch even with normal plasma homocysteine levels. Mice fed B vitamin-deficient diets developed severe hyperhomocysteinemia but without any increase in vascular pathology. Our findings suggest that even moderate increases in methionine intake are atherogenic in susceptible mice while high plasma homocysteine is not.
当研究表明，在蛋氨酸负荷后，心血管疾病患者的循环同型半胱氨酸-半胱氨酸浓度高于健康对照组时，同型半胱氨酸致动脉硬化理论得到了认可。随后的研究表明，同型半胱氨酸与冠心病、中风和认知障碍之间存在关联，这依赖于同型半胱氨酸浓度的小幅度增加，而不是在罕见的遗传疾病中所见的导致高同型半胱氨酸血症的非常高的同型半胱氨酸。随后在细胞培养、动物和人类中的研究表明，“高同型半胱氨酸”的各种心血管不良影响，无论是作为非生理性冲击还是蛋氨酸负荷引入，都会导致同型半胱氨酸升高。我们用设计的饮食喂养载脂蛋白 E 缺陷型小鼠，以达到三种条件：（1）高蛋氨酸摄入和正常血液同型半胱氨酸，（2）高蛋氨酸摄入和 B 族维生素缺乏及高同型半胱氨酸血症，（3）正常蛋氨酸摄入和 B 族维生素缺乏及高同型半胱氨酸血症。我们发现，即使血浆同型半胱氨酸水平正常，喂食富含蛋氨酸饮食的小鼠在主动脉弓中也有明显的动脉粥样硬化病变。喂食 B 族维生素缺乏饮食的小鼠会发生严重的高同型半胱氨酸血症，但血管病变没有增加。我们的研究结果表明，即使适度增加蛋氨酸摄入也会使易感小鼠产生动脉粥样硬化，而高血浆同型半胱氨酸则不会。
