Atheroprotective mechanisms of shear stress-regulated microRNAs
Atheroprotective mechanisms of shear stress-regulated microRNAs
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DOI：
10.1160/th12-07-0491
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发表时间：
2012-10-01
影响因子：
6.7
通讯作者：
Dimmeler, Stefanie
中科院分区：
文献类型：
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作者：
Boon, Reinier A.;Hergenreider, Eduard;Dimmeler, Stefanie
microRNA（miRs）是通过抑制靶mRNA的翻译或诱导靶mRNA的降解来控制基因表达的小的非编码RNA。miR不仅在血管稳态中而且在病理生理过程中起关键作用。功能活跃的内皮细胞维持血管系统的稳态，并防止心血管疾病。通过层流剪切应力对内皮细胞的机械活化提供了有效的动脉粥样硬化保护作用，并减少了内皮炎症和细胞周期进展。层流剪切应力诱导基因表达的深刻变化，最近被证明可以调节各种miR。剪切力下调miR-92 a可增强内皮型一氧化氮合酶的表达，而上调miR-19 a则有助于剪切力诱导的细胞增殖抑制。此外，miR-23-27-24簇的成员增加，特别是miR-23 b阻断细胞周期进程，而miR-27 b显示减少内皮细胞排斥信号。最后，在动脉粥样硬化保护区域中增加的miR-10表达降低了内皮细胞的炎症反应，并且增加内皮miR-143/145水平改善了平滑肌细胞功能。总之，剪切应力对miR的调节有助于内皮细胞中的抗炎、细胞周期抑制和血管保护作用。
MicroRNAs (miRs) are small non-coding RNAs that control gene expression by inhibiting translation or inducing degradation of targeted mRNA. miRs play a crucial role in vascular homeostasis but also during pathophysiological processes. Functionally active endothelial cells maintain homeostasis of the vasculature and protect against cardiovascular disease. The mechanical activation of endothelial cells by laminar shear stress provides a potent atheroprotective effect and reduces endothelial inflammation and cell cycle progression. Laminar shear stress induces profound changes in gene expression and recently was shown to regulate various miRs. The down-regulation of miR-92a by shear stress enhances the expression of the endothelial nitric oxide synthase, whereas the up-regulation of miR-19a contributes to the shear stressinduced inhibition of cell proliferation. In addition, members of the miR-23-27-24 cluster are increased and specifically miR-23b blocks cell cycle progression, whereas miR-27b was shown to reduce endothelial cell repulsive signals. Finally, increased miR-10 expression in athero-protected regions reduced the inflammatory response of endothelial cells and increased endothelial miR-143/145 levels improved smooth muscle cells functions. Together, the regulation of miRs by shear stress contributes to the anti-inflammatory, cell cycle inhibitory and vasculoprotective effects in endothelial cells.