Homocysteine accelerates atherosclerosis by inhibiting scavenger receptor class B member1 via DNMT3b/SP1 pathway
Homocysteine accelerates atherosclerosis by inhibiting scavenger receptor class B member1 via DNMT3b/SP1 pathway
复制标题
同型半胱氨酸通过 DNMT3b/SP1 通路抑制清道夫受体 B 类成员 1 加速动脉粥样硬化
DOI：
10.1016/j.yjmcc.2019.11.145
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发表时间：
2020-01-01
影响因子：
5
通讯作者：
Jiang, Yideng
中科院分区：
文献类型：
--
作者：
Guo, Wei;Zhang, Huiping;Jiang, Yideng
同型半胱氨酸（Homocysteine，Hcy）是动脉粥样硬化的独立危险因素，其特征是脂质在动脉粥样硬化斑块中的积聚。越来越多的证据表明，作为高密度脂蛋白的主要受体，清道夫受体B类成员1（SCARB 1）对动脉粥样硬化具有保护作用。然而，其在Hcy介导的动脉粥样硬化中的潜在机制仍不清楚。在这里，我们发现了显着的抑制SCARB 1表达的动脉粥样硬化斑块和Hcy处理的泡沫细胞，而过表达的SCARB 1可以抑制泡沫细胞中的脂质积累后，Hcy治疗。对SCARB 1基因启动子甲基化水平的分析表明，在体内和体外Hcy处理下，SCARB 1基因启动子甲基化水平均无明显变化。此外，发现DNMT 3b对SCARB 1的负调控是由于SP1对SCARB 1启动子的募集减少。因此，我们得出结论，DNMT 3b诱导的SCARB 1表达的抑制至少部分地通过促进泡沫细胞中的脂质积聚来加速Hcy介导的动脉粥样硬化，这归因于SP1与SCARB 1启动子的结合减少。在我们看来，这些发现将为动脉粥样硬化的表观遗传机制提供新的见解。
Homocysteine (Hcy) is an independent risk factor for atherosclerosis, which is characterized by lipid accumulation in the atherosclerotic plaque. Increasing evidence supports that as the main receptor of high-density lipoprotein, scavenger receptor class B member 1 (SCARB1) is protective against atherosclerosis. However, the underlying mechanism regarding it in Hcy-mediated atherosclerosis remains unclear. Here, we found the remarkable inhibition of SCARB1 expression in atherosclerotic plaque and Hcy-treated foam cells, whereas overexpression of SCARB1 can suppress lipid accumulation in foam cells following Hcy treatment. Analysis of SCARB1 promoter showed that no significant change of methylation level was observed both in vivo and in vitro under Hcy treatment. Moreover, it was found that the negative regulation of DNMT3b on SCARB1 was due to the decreased recruitment of SP1 to SCARB1 promoter. Thus, we concluded that inhibition of SCARB1 expression induced by DNMT3b at least partly accelerated Hcy-mediated atherosclerosis through promoting lipid accumulation in foam cells, which was attributed to the decreased binding of SP1 to SCARB1 promoter. In our point, these findings will provide novel insight into an epigenetic mechanism for atherosclerosis.