Betaine supplementation attenuates atherosclerotic lesion in apolipoprotein E-deficient mice
Betaine supplementation attenuates atherosclerotic lesion in apolipoprotein E-deficient mice
复制标题
补充甜菜碱可减轻载脂蛋白 E 缺陷小鼠的动脉粥样硬化病变
DOI：
10.1007/s00394-009-0003-4
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发表时间：
2009-06-01
影响因子：
5
通讯作者：
Zhu, Huilian
中科院分区：
文献类型：
--
作者：
Lv, Shiwei;Fan, Ruixin;Zhu, Huilian
甜菜碱在同型半胱氨酸转化为蛋氨酸的反应中充当甲基供体。它通常用于治疗人类高同型半胱氨酸血症，这表明它可能与降低动脉粥样硬化风险有关。然而，关于其血管作用的资料很少。探讨补充甜菜碱对载脂蛋白e缺陷小鼠动脉粥样硬化损伤的影响。四组apoe缺陷小鼠饲喂AIN-93G饲粮，添加0、1、2或4 g甜菜碱/100 g饲粮（分别为no、1、2和4%甜菜碱）。饲喂野生型C57BL/6 J小鼠AIN-93G日粮（野生型）。小鼠在实验饮食0、7、14周后被处死。测定主动脉窦动脉粥样硬化病变区域、主动脉和血清中肿瘤坏死因子(TNF)- α和单核细胞趋化蛋白(MCP)-1水平、血脂和主动脉中TNF- α启动子甲基化状态。线性回归分析显示，甜菜碱剂量越大，动脉粥样硬化病变面积越小（β = -11.834, P < 0.001）。14周后，与未服用甜菜碱的小鼠相比，服用1%、2%和4%甜菜碱的小鼠病变面积分别缩小了10.8%、41%和37%。在四组apoe缺陷小鼠中，补充甜菜碱也以剂量依赖的方式降低了主动脉中tnf - α的表达，Pearson相关性显示动脉粥样硬化病变面积与主动脉中tnf - α水平呈正相关（r = 0.777, P < 0.001）。虽然在治疗14周后，添加甜菜碱的小鼠血清tnf - α水平低于未添加甜菜碱的小鼠（P < 0.001），但我们没有观察到显著的剂量效应（P = 0.11）。然而，tnf - α启动子的甲基化水平在任何时间组间没有差异。在本研究中，补充甜菜碱14周的apoe缺陷小鼠血清总胆固醇（P < 0.01）、低密度脂蛋白胆固醇（P < 0.05）浓度高于未补充甜菜碱小鼠（P < 0.05），体重低于未补充甜菜碱小鼠（P < 0.05）。这些数据表明，尽管加重了apoe缺陷小鼠的高脂血症，甜菜碱可能通过抑制tnf - α介导的主动脉炎症反应来发挥其抗动脉粥样硬化作用。
Betaine serves as a methyl donor in a reaction converting homocysteine to methionine. It is commonly used for the treatment of hyperhomocysteinemia in humans, which indicates it may be associated with reduced risk of atherosclerosis. However, there have been few data regarding its vascular effect.To investigate the effect of betaine supplementation on atherosclerotic lesion in apolipoprotein (apo) E-deficient mice.Four groups of apoE-deficient mice were fed AIN-93G diets supplemented with 0, 1, 2, or 4 g betaine/100 g diet (no, 1, 2, and 4% betaine, respectively). Wild-type C57BL/6 J mice were fed AIN-93G diet (wild-type). Mice were sacrificed after 0, 7, or 14 weeks of the experimental diets. Atherosclerotic lesion area in the aortic sinus, levels of tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein (MCP)-1 in aorta and serum, serum lipids, and methylation status of TNF-alpha promoter in aorta were determined.Linear regression analysis showed that the higher dose of betaine was related to smaller atherosclerotic lesion area (beta = -11.834, P < 0.001). Compared with no-betaine mice after 14 weeks, mice receiving 1%, 2%, or 4% betaine had 10.8, 41, and 37% smaller lesion area, respectively. Betaine supplementation also reduced aortic expression of TNF-alpha in a dose-dependent way in four groups of apoE-deficient mice, and Pearson correlation revealed that atherosclerotic lesion area was positively associated with aortic TNF-alpha level (r = 0.777, P < 0.001). Although serum TNF-alpha levels were lower in betaine-supplemented mice than in no-betaine mice after fourteen weeks of treatment (P < 0.001), we did not observe a significant dosage effect (P = 0.11). However, methylation level of TNF-alpha promoter did not differ among groups at any time. In this study, apoE-deficient mice receiving betaine supplementation for 14 weeks had higher concentrations of serum total cholesterol (P < 0.01), LDL cholesterol (P < 0.05), and lower body weight (P < 0.05) than no-betaine mice.These data suggest that despite exacerbating hyperlipidemia in apoE-deficient mice, betaine may exert its anti-atherogenic effect by inhibiting aortic inflammatory response mediated by TNF-alpha.