Plasma S-adenosylhomocysteine is a better biomarker of atherosclerosis than homocysteine in apolipoprotein E-deficient mice fed high dietary methionine
Plasma S-adenosylhomocysteine is a better biomarker of atherosclerosis than homocysteine in apolipoprotein E-deficient mice fed high dietary methionine
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在喂食高膳食蛋氨酸的载脂蛋白 E 缺陷小鼠中，血浆 S-腺苷同型半胱氨酸是比同型半胱氨酸更好的动脉粥样硬化生物标志物。
DOI：
10.1093/jn/138.2.311
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发表时间：
2008-02-01
影响因子：
4.2
通讯作者：
Ling, Wenhua
中科院分区：
文献类型：
--
作者：
Liu, Chi;Wang, Qing;Ling, Wenhua
同型半胱氨酸(Hcy)和S腺苷同型半胱氨酸(ADOHcy)是蛋氨酸代谢的重要中间产物。为了研究这些化合物中的哪一种与动脉粥样硬化关系更密切，我们给5组载脂蛋白E(ApoE)缺陷小鼠喂食不同饮食8周，以诱导它们血浆Hcy和Adobe Hcy浓度的变化。其中包括AIN-93G对照饮食(C)、添加蛋氨酸(M)的C饮食、缺乏叶酸、维生素B-6和维生素B-12(M-V)的M饮食、补充这些B维生素的M饮食(M+V)和缺乏B维生素的C饮食(C-V)。与对照组相比，饲喂C-V饮食的小鼠血浆总同型半胱氨酸(THcy)水平有中等程度的升高，但它们的血浆ADHcy浓度和动脉粥样硬化病变面积没有差异。相比之下，饲喂M+V饮食的小鼠有更大的动脉粥样硬化病变面积和升高的血浆ADHcy浓度，但其血浆tHcy浓度与C组小鼠没有差异。血浆ADO-Hcy浓度与主动脉窦病变面积呈正相关(r=0.866；P<；0.001)。我们观察到血浆ADOHcy浓度与主动脉组织中DNA甲基转移酶活性(r=-0.792；P<；0.001)和整体DNA甲基化状态(r=-0.824；P<；0.001)呈负相关。因此，我们的研究表明，血浆ADOHcy是比Hcy更好的动脉粥样硬化的生物标志物，并且可能加速高蛋氨酸饮食的apoE缺陷小鼠的动脉粥样硬化病变的发展。这种作用的机制可能与ADOHcy介导的抑制主动脉组织DNA甲基化有关。
Homocysteine (Hcy) and S-adenosylhomocysteine (AdoHcy) are critical intermediates of methionine metabolism. To investigate which, if either, of these compounds is more closely related to atherosclerosis, we fed 5 groups of apolipoprotein E (apoE)-deficient mice different diets for 8 wk to induce changes in their plasma Hcy and AdoHcy concentrations. These included an AIN-93G control diet (C), this C diet supplemented with methionine (M), the M diet deficient in folates, vitamin B-6, and vitamin B-12 (M-V), this M diet supplemented with these B vitamins (M+V), and a C diet deficient in B vitamins (C-V). Compared with controls, mice fed the C-V diet had a moderate elevation in their plasma total Hcy (tHcy) levels; however, their plasma AdoHcy concentration and atherosclerotic lesion areas were not different. In contrast, the mice fed the M+V diet had larger atherosclerotic lesion areas and elevated plasma AdoHcy concentrations but their plasma tHcy concentration did not differ from that of the group C mice. The plasma AdoHcy concentration and aortic sinus lesion areas were positively correlated (r = 0.866; P < 0.001). We observed a negative correlation between the plasma AdoHcy concentration and both the DNA methyltransferase activity (r = -0.792; P < 0.001) and global DNA methylation status (r = -0.824; P < 0.001) in the aortic tissue. Hence, our study suggests that plasma AdoHcy is a better biomarker of atherosclerosis than Hcy and may accelerate the development of atherosclerotic lesions in apoE-deficient mice that have been fed a high methionine diet. The mechanisms underlying this effect may be related to the AdoHcy-mediated inhibition of DNA methylation in the aortic tissue.