Endothelial epigenetics in biomechanical stress: disturbed flow-mediated epigenomic plasticity in vivo and in vitro.
Endothelial epigenetics in biomechanical stress: disturbed flow-mediated epigenomic plasticity in vivo and in vitro.
复制标题
DOI：
10.1161/atvbaha.115.303427
复制
发表时间：
2015-06
期刊：
影响因子：
--
通讯作者：
Davies PF
中科院分区：
文献类型：
--
作者：
Jiang YZ;Manduchi E;Jiménez JM;Davies PF
动脉内皮细胞表型受局部血流动力学的调节，而局部血流动力学与动脉粥样硬化的易感性有关。一个复杂的层次的转录，翻译和翻译后的机制，极大地影响了当地动脉切应力环境的特点。我们讨论了局部扰动血流在内皮细胞对生物力学应力反应的表观遗传机制中的作用，包括近端启动子DNA甲基化的转录调控，染色质重塑和非编码RNA机制对基因和蛋白质表达的转录后和翻译调控。在体内和体外的流动特性的动态响应包括位点特异性差异甲基化区域的猪和小鼠内皮甲基化，组蛋白标志物调节染色质构象，microRNA和长的非编码RNA。血流介导的表观基因组反应与顺式和反式因子调节交叉，以维持剪切应激环境中的内皮功能，并可能导致局部内皮功能障碍，从而促进动脉粥样硬化易感性。
Arterial endothelial phenotype is regulated by local hemodynamic forces that are linked to regional susceptibility to atherogenesis. A complex hierarchy of transcriptional, translational and posttranslational mechanisms are greatly influenced by the characteristics of local arterial shear stress environments. We discuss the emerging role of localized disturbed blood flow upon epigenetic mechanisms of endothelial responses to biomechanical stress, including transcriptional regulation by proximal promoter DNA methylation, and posttranscriptional and translational regulation of gene and protein expression by chromatin remodeling and noncoding RNA-based mechanisms. Dynamic responses to flow characteristics in vivo and in vitro include site-specific differentially methylated regions of swine and mouse endothelial methylomes, histone marks regulating chromatin conformation, microRNAs and long noncoding RNAs. Flow-mediated epigenomic responses intersect with cis and trans factor regulation to maintain endothelial function in a shear-stressed environment and may contribute to localized endothelial dysfunctions that promote atherosusceptibility.