The Yin-Yang Dynamics of DNA Methylation Is the Key Regulator for Smooth Muscle Cell Phenotype Switch and Vascular Remodeling
The Yin-Yang Dynamics of DNA Methylation Is the Key Regulator for Smooth Muscle Cell Phenotype Switch and Vascular Remodeling
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DOI：
10.1161/atvbaha.116.307923
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发表时间：
2017-01-01
影响因子：
8.7
通讯作者：
Peng, Wenhui
中科院分区：
文献类型：
--
作者：
Zhuang, Jianhui;Luan, Peipei;Peng, Wenhui
DNA甲基化在动脉粥样硬化等慢性疾病中起着重要作用，但其机制尚不清楚。本研究的目的是阐明血管平滑肌细胞（VSMCs）DNA甲基化的调控机制及其在动脉粥样硬化中的作用。方法和结果：在ApoE（-/-）小鼠中，DNA甲基转移酶抑制剂5-氮杂-2 '-脱氧胞苷（5-aza-2'-deoxycytidine，5-de（20.1+/-2.2%对30.8+/-7.5%; P=0.016），抑制DNA甲基转移酶活性，同时降低ApoE（-/-）小鼠动脉粥样硬化病变中的总体5-甲基胞嘧啶含量。使用颈动脉结扎模型，我们发现5-氮杂-2 '-脱氧胞苷也显著抑制新生内膜形成（内膜面积：2.25+/-0.14x10（4）对4.07+/-0.22x10（4）μ m（2）; P
Objective-DNA methylation plays an important role in chronic diseases such as atherosclerosis, yet the mechanisms are poorly understood. The objective of our study is to indicate the regulatory mechanisms of DNA methylation in vascular smooth muscle cells (VSMCs) and its roles in atherosclerosis.Approach and Results-In ApoE(-/-) mice fed a Western diet, DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, significantly attenuated atherosclerotic lesions (20.1+/-2.2% versus 30.8+/-7.5%; P=0.016) and suppressed DNA methyltransferase activity and concomitantly decreased global 5-methylcytosine content in atherosclerotic lesions of ApoE(-/-) mice. Using a carotid ligation model, we found that 5-aza-2'-deoxycytidine also dramatically inhibited neointimal formation (intimal area: 2.25+/-0.14x10(4) versus 4.07+/-0.22x10(4) mu m(2); P