Mechanosensitive microRNAs-role in endothelial responses to shear stress and redox state.

Mechanosensitive microRNAs-role in endothelial responses to shear stress and redox state.
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DOI:
10.1016/j.freeradbiomed.2013.05.034
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发表时间:
2013-09
影响因子:
7.4
通讯作者:
Shyy, John Y. -J.
Shyy, John Y. -J.
中科院分区:
医学1区
文献类型:
--
作者:
Marin, Traci;Gongol, Brendan;Chen, Zhen;Woo, Brian;Subramaniam, Shankar;Chien, Shu;Shyy, John Y. -J.

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在体内,内皮功能受到施加的剪切应力的高度调节。剪切应力的特性决定了调节表型结果(包括氧化还原和炎症状态)的机械转导事件。最近的研究表明,血管内皮细胞(ECs)中的microRNAs(miRs)在切应力调节内皮细胞反应中起着重要作用。更具体地,动脉粥样硬化保护性脉动流(PS)诱导miR,其抑制氧化应激和炎症的介质,同时促进参与维持血管稳态的介质。相反,振荡流(OS)消除了相反的网络。这由PS响应性转录因子Krueppel样因子2(KLF2)例示,其调节miR表达,但也由OS敏感性miR调节以最终调节内皮的氧化和炎症状态。在这篇综述中,我们概述了重要的研究结果,证明了剪切应力调节的miR在内皮细胞氧化还原和炎症平衡中的多方面作用。此外,我们讨论了使用的算法在破译信号网络的差异调节PS和OS。
Endothelial functions are highly regulated by imposed shear stress in vivo. The characteristics of shear stress determine mechanotransduction events that regulate phenotypic outcomes including redox and inflammatory states. Recent data indicates that microRNAs (miRs) in vascular endothelial cells (ECs) play an essential role in shear stress-regulated endothelial responses. More specifically, athero-protective pulsatile flow (PS) induces miRs that inhibit mediators of oxidative stress and inflammation while promoting those involved in maintaining vascular homeostasis. Conversely, oscillatory flow (OS) elicits the opposing networks. This is exemplified by the PS-responsive transcription factor, krueppel-like factor 2 (KLF2), which regulates miR expression but is also regulated by OS-sensitive miRs to ultimately regulate the oxidative and inflammatory state of the endothelium. In this review, we outline important findings demonstrating the multifaceted roles of shear stress-regulated miRs in endothelial redox and inflammatory balance. Furthermore, we discuss the use of algorithms in deciphering signaling networks differentially regulated by PS and OS.
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