Mild folate deficiency induces a proatherosclerotic phenotype in endothelial cells
Mild folate deficiency induces a proatherosclerotic phenotype in endothelial cells
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DOI：
10.1016/j.atherosclerosis.2005.12.018
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发表时间：
2006-11-01
期刊：
影响因子：
5.3
通讯作者：
Whitehead, Alexander S.
中科院分区：
文献类型：
--
作者：
Brown, Karen S.;Huang, Yuehua;Whitehead, Alexander S.
低叶酸/高同型半胱氨酸（Hey）是心血管疾病（CVD）的危险标志。一些体内研究表明，低叶酸可能单独导致心血管疾病。为了研究轻度叶酸缺乏对内皮细胞功能的影响，我们将EA.hy 926内皮细胞置于含有23 nM叶酸（LO细胞）或9 μ M叶酸（HI细胞）的培养基中生长。相对于HI细胞，LO细胞中叶酸衍生物大量减少。在细胞内同型半胱氨酸、s -腺苷蛋氨酸（SAM）、s -腺苷同型半胱氨酸（SAH）、SAM:SAH比率或整体DNA甲基化方面没有差异，分泌的同型半胱氨酸也没有一致的差异。处于细胞周期S期的LO细胞比例高于HI细胞；在LO细胞中补充胸腺嘧啶/次黄嘌呤可以防止这种情况。低脂细胞比高脂细胞更细长，不形成紧密的单层。应力纤维在LO细胞中非常突出，而在HI细胞中不明显。用rho激酶抑制剂处理LO细胞可消除应力纤维并使细胞形状部分正常化。低脂细胞单层比HI细胞单层更具渗透性，低脂细胞中MCP-1 mRNA和蛋白的表达高于HI细胞。我们的研究结果表明轻度叶酸缺乏会促进动脉粥样硬化。2005爱思唯尔爱尔兰有限公司版权所有。
Low folate/high homocysteine (Hey) is an established risk marker for cardiovascular disease (CVD). Some in vivo studies suggest low folate may independently contribute to CVD. To study the effects of mild folate deficiency on endothelial function, we adapted the EA.hy 926 endothelial cell line to growth in medium containing 23 nM folic acid (LO cells) or 9 mu M folic acid (HI cells). Folate derivatives were substantially depleted in LO cells relative to HI cells. No differences were seen in intracellular homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), the SAM:SAH ratio, or global DNA methylation, and there was no consistent difference in secreted homocysteine. A greater percentage of LO than HI cells were in S phase of the cell cycle; supplementation of LO cells with thymidine/hypoxanthine prevented this. LO cells were more elongated than HI cells and did not form tight monolayers. Stress fibers were very prominent in LO but not HI cells. Treatment of LO cells with rho kinase inhibitors abolished stress fibers and partially normalized cell shape. LO cell monolayers were more permeable than HI cell monolayers at confluence, and MCP-1 mRNA and protein expression was higher in LO than HI cells. Our results suggest that mild folate deficiency is proatherosclerotic. (c) 2005 Elsevier Ireland Ltd. All rights reserved.