Mechanoresponsive Networks Controlling Vascular Inflammation
Mechanoresponsive Networks Controlling Vascular Inflammation
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DOI：
10.1161/atvbaha.114.303424
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发表时间：
2014-10-01
影响因子：
8.7
通讯作者：
Evans, Paul C.
中科院分区：
文献类型：
--
作者：
Bryan, Matthew T.;Duckles, Hayley;Evans, Paul C.
动脉粥样硬化是一种动脉慢性炎症性疾病，优先发生在暴露于血流紊乱的分支和弯曲处。血管功能通过流动来改变，部分地通过产生改变内皮细胞中多种生理过程的机械力来改变。剪切应力对血管炎症有深远的影响;高均匀剪切应力通过减少粘附分子和其他炎性蛋白的内皮表达来防止白细胞募集到血管壁，而低振荡剪切应力具有相反的效果。在这里，我们审查的分子机制，支持切应力对内皮炎症反应的影响。它们包括炎性丝裂原活化蛋白激酶和核因子-κ B信号传导的剪切应力调节。高剪切通过诱导几种炎症负调节因子来抑制这些通路，而低剪切促进炎症信号传导。此外，我们总结了最近的研究表明，炎症信号是非常敏感的脉搏波的频率，幅度和流动方向。最后，系统生物学方法（包括组学研究和功能筛选），以确定新的机械敏感途径的重要性进行了讨论。
Atherosclerosis is a chronic inflammatory disease of arteries that develops preferentially at branches and bends that are exposed to disturbed blood flow. Vascular function is modified by flow, in part, via the generation of mechanical forces that alter multiple physiological processes in endothelial cells. Shear stress has profound effects on vascular inflammation; high uniform shear stress prevents leukocyte recruitment to the vascular wall by reducing endothelial expression of adhesion molecules and other inflammatory proteins, whereas low oscillatory shear stress has the opposite effects. Here, we review the molecular mechanisms that underpin the effects of shear stress on endothelial inflammatory responses. They include shear stress regulation of inflammatory mitogen-activated protein kinase and nuclear factor-kappa B signaling. High shear suppresses these pathways through the induction of several negative regulators of inflammation, whereas low shear promotes inflammatory signaling. Furthermore, we summarize recent studies indicating that inflammatory signaling is highly sensitive to pulse wave frequencies, magnitude, and direction of flow. Finally, the importance of systems biology approaches (including omics studies and functional screening) to identify novel mechanosensitive pathways is discussed.