Usui M, Matsuoka H, Miyazaki H, Ueda S, Okuda S, Imaizumi T
Department of Internal Medicine III, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011 Japan.
Clin Sci (Lond). 1999 Mar;96(3):235-9.
Recent evidence demonstrates that hyperhomocyst(e)inaemia is a novel risk factor for cardiovascular diseases. In patients with chronic hyperhomocyst(e)inaemia, endothelial function is impaired. However, whether hyperhomocyst(e)inaemia per se is a cause or an epiphenomenon of endothelial dysfunction remains unknown. In this study, we examined the effects of methionine-induced acute hyperhomocyst(e)inaemia on human endothelial function. In healthy volunteers we administered methionine (0.1 g/kg body weight, per os), a substrate of homocyst(e)ine, with or without folic acid (20 mg, per os) and examined flow-mediated vasodilatation of the brachial artery by high-resolution ultrasonography as a non-invasive measure of endothelial function. We also measured plasma levels of homocyst(e)ine before and 3, 8 and 24 h after methionine loading. Methionine administration increased plasma levels of homocyst(e)ine by four times the basal level at 8 h (P<0.0001, ANOVA). The plasma levels returned to baseline at 24 h. Flow-mediated vasodilatation was significantly decreased to half of the baseline value at 8 h and returned to baseline at 24 h (P<0.0001, ANOVA), whereas endothelium-independent vasodilatation by glyceryl trinitrate was not affected by the methionine loading. Co-administration of folic acid did not attenuate methionine-induced hyperhomocyst(e)inaemia but completely prevented endothelial dysfunction. Our results suggest that in humans a methionine-rich diet may acutely impair endothelial function, which can be prevented by folic acid supplementation.
近期证据表明，高同型半胱氨酸血症是心血管疾病的一个新的危险因素。在慢性高同型半胱氨酸血症患者中，内皮功能受损。然而，高同型半胱氨酸血症本身是内皮功能障碍的原因还是一种附带现象仍不清楚。在本研究中，我们检测了蛋氨酸诱导的急性高同型半胱氨酸血症对人类内皮功能的影响。在健康志愿者中，我们口服给予同型半胱氨酸的底物蛋氨酸（0.1 g/kg体重），同时给予或不给予叶酸（20 mg，口服），并通过高分辨率超声检查肱动脉的血流介导的血管舒张，以此作为内皮功能的一种非侵入性测量方法。我们还在蛋氨酸负荷前以及负荷后3、8和24小时测量了血浆同型半胱氨酸水平。给予蛋氨酸后，8小时时血浆同型半胱氨酸水平升高至基础水平的四倍（P<0.0001，方差分析）。24小时时血浆水平恢复至基线。血流介导的血管舒张在8小时时显著降低至基线值的一半，并在24小时时恢复至基线（P<0.0001，方差分析），而硝酸甘油介导的非内皮依赖性血管舒张不受蛋氨酸负荷的影响。同时给予叶酸并不能减轻蛋氨酸诱导的高同型半胱氨酸血症，但能完全预防内皮功能障碍。我们的结果表明，在人类中，富含蛋氨酸的饮食可能会急性损害内皮功能，而补充叶酸可以预防这种损害。
