Endothelial dysfunction by acute hyperhomocyst(e)inaemia: restoration by folic acid
Endothelial dysfunction by acute hyperhomocyst(e)inaemia: restoration by folic acid
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DOI：
10.1042/cs19980382
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发表时间：
1999-03-01
期刊：
影响因子：
6
通讯作者：
Imaizumi, T
中科院分区：
文献类型：
--
作者：
Usui, M;Matsuoka, H;Imaizumi, T
最近的证据表明，高同型半胱氨酸血症是心血管疾病的新危险因素。慢性高同型囊肿血症患者的内皮功能受损。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附带现象仍不清楚。在这项研究中，我们研究了蛋氨酸诱导的急性高同型半胱氨酸血症对人内皮功能的影响。在健康志愿者中，我们给予蛋氨酸（0.1克/公斤体重，每次口服），一种同型半胱氨酸的底物，加或不加叶酸（20毫克，每次口服），并通过高分辨率超声检查检查肱动脉的血流介导的血管舒张，作为内皮功能的非侵入性测量。我们还测量了甲硫氨酸加载前以及加载后 3、8 和 24 小时的血浆同型半胱氨酸水平。施用蛋氨酸后 8 小时，血浆同型半胱氨酸水平增加至基础水平的四倍（P < 0.0001，方差分析）。 24小时后血浆水平恢复至基线。血流介导的血管舒张在 8 小时时显着降至基线值的一半，并在 24 小时时恢复到基线值（P < 0.0001，方差分析），而三硝酸甘油的内皮依赖性血管舒张不受蛋氨酸负荷的影响。给予叶酸并不能减轻蛋氨酸诱导的高同型半胱氨酸血症，但可以完全预防内皮功能障碍。我们的研究结果表明，人类富含蛋氨酸的饮食可能会严重损害内皮功能，这可以通过补充叶酸来预防。
Recent evidence demonstrates that hyperhomocyst(e)inaemia is a novel risk factor for cardiovascular diseases. In patients with chronic hy perhomocyst(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. Go-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.