Homocysteine-induced proliferation of vascular smooth muscle cells occurs via PTEN hypermethylation and is mitigated by Resveratrol
Homocysteine-induced proliferation of vascular smooth muscle cells occurs via PTEN hypermethylation and is mitigated by Resveratrol
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同型半胱氨酸诱导的血管平滑肌细胞增殖是通过 PTEN 高甲基化发生的，白藜芦醇可以减轻这种增殖
DOI：
10.3892/mmr.2018.8471
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发表时间：
2018-04-01
影响因子：
3.4
通讯作者：
Jiang, Yi-Deng
中科院分区：
文献类型：
--
作者：
Ma, Sheng-Chao;Zhang, Hui-Ping;Jiang, Yi-Deng
血管平滑肌细胞（VSMC）增殖是动脉粥样硬化（AS）发生发展的主要病理过程，同型半胱氨酸（Hcy）是AS的独立危险因素。然而，其潜在机制仍有待阐明。10号染色体上的磷酸酶和张力蛋白同源物（Phosphatase and tensin homologue on chromosome 10，PTEN）在血管平滑肌细胞中内源性表达，并诱导多种信号网络参与细胞增殖、存活和炎症，但其具体作用尚不清楚。本研究检测了同型半胱氨酸（Hcy）和白藜芦醇（Resveratrol，RSV）对VSMCs增殖的影响。在100 μ M Hcy组中，增殖率增加，RSV处理降低Hcy诱导的增殖率。逆转录-定量聚合酶链反应和蛋白质印迹法检测VSMCs中PTEN的表达，RSV处理组VSMCs中PTEN的表达水平降低。Hcy处理后，VSMCs增殖率增加，PTEN表达降低。为了研究Hcy对PTEN的调控机制，本研究检测了VSMCs中PTEN的甲基化水平，结果显示100 μ M Hcy组PTEN DNA甲基化水平升高，而RSV处理组则降低了甲基化水平。DNA甲基转移酶1在调节PTEN甲基化中起重要作用。总之，Hcy影响参与细胞增殖的PTEN的甲基化状态，并诱导VSMC增殖。这种作用通过用RSV治疗而减轻，RSV表现出针对Hcy的拮抗机制。
Vascular smooth muscle cell (VSMC) proliferation is a primary pathological event in the development of atherosclerosis (AS), and the presence of homocysteine (Hcy) acts as an independent risk factor for AS. However, the underlying mechanisms remain to be elucidated. Phosphatase and tensin homologue on chromosome 10 (PTEN), is endogenously expressed in VSMCs and induces multiple signaling networks involved in cell proliferation, survival and inflammation, however, the specific role of PTEN is still unknown. The present study detected the proliferation ratio of VSMCs following treatment with Hcy and Resveratrol (RSV). In the 100 mu M Hcy group, the proliferation ratio increased, and treatment with RSV decreased the proliferation ratio induced by Hcy. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to analyze PTEN expression, RSV treatment was associated with decreased PTEN expression levels in VSMCs. PTEN levels were decreased in Hcy treated cells, and the proliferation ratio of VSMCs were increased following treated with Hcy. To study the mechanism of regulation of PTEN by Hcy, the present study detected PTEN methylation levels in VSMCs, and PTEN DNA methylation levels were demonstrated to be increased in the 100 mu M Hcy group, whereas treatment with RSV decreased the methylation status. DNA methyltransferase 1 is important role in the regulation of PTEN methylation. Overall, Hcy impacts the methylation status of PTEN, which is involved in cell proliferation, and induces the proliferation of VSMCs. This effect is alleviated by treatment with RSV, which exhibits an antagonistic mechanism against Hcy.