Non-coding RNAs in cerebral endothelial pathophysiology: emerging roles in stroke.

Non-coding RNAs in cerebral endothelial pathophysiology: emerging roles in stroke.
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DOI:
10.1016/j.neuint.2014.03.013
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发表时间:
2014-11
影响因子:
4.2
通讯作者:
Chen YE
Chen YE
中科院分区:
医学3区
文献类型:
--
作者:
Yin KJ;Hamblin M;Chen YE

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脑血管内皮细胞是血脑屏障(BBB)的主要组成部分,是循环血液和脑实质之间的主要界面。众所周知,脑缺血期间脑内皮的结构和功能变化导致BBB破坏、血管炎症、水肿和血管生成。这些复杂的病理过程直接导致脑梗死、神经功能缺损和卒中后神经血管重塑。缺血性内皮功能障碍似乎受到多个基因信号网络的严格控制。非编码RNA(Non-coding RNA,ncRNA)是一种功能性RNA分子,通常不翻译成蛋白质,但可以通过不同的机制主动调节成千上万个蛋白质编码基因的表达和功能。各种类型的ncRNA,包括microRNA(miRNAs)、长非编码RNA(lncRNA)、小核仁RNA(snoRNA)和piwi相互作用RNA(piRNA),在脑血管内皮中高度表达,其中它们充当维持正常脑血管功能的关键介质。ncRNA活性的失调与脑血管内皮的病理生理学和脑对缺血刺激的反应中的神经功能障碍密切相关。本文综述了这些ncRNA介导物在脑血管系统中的最新研究进展,重点介绍了内皮细胞miRNAs在脑卒中中的特殊作用。
Cerebral vascular endothelial cells form the major element of the blood-brain barrier (BBB) and constitute the primary interface between circulating blood and brain parenchyma. The structural and functional changes in cerebral endothelium during cerebral ischemia are well known to result in BBB disruption, vascular inflammation, edema, and angiogenesis. These complex pathological processes directly contribute to brain infarction, neurological deficits, and post-stroke neurovascular remodeling. Ischemic endothelial dysfunction appears to be tightly controlled by multiple gene signaling networks. Non-coding RNAs (ncRNAs) are functional RNA molecules that are generally not translated into proteins but can actively regulate the expression and function of many thousands of protein-coding genes by different mechanisms. Various classes of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), small nucleolar RNAs (snoRNAs) and piwi-interacting RNAs (piRNAs), are highly expressed in the cerebrovascular endothelium where they serve as critical mediators to maintain normal cerebral vascular functions. Dysregulation of ncRNA activities has been closely linked to the pathophysiology of cerebral vascular endothelium and neurologic functional disorders in the brain’s response to ischemic stimuli. In this review, we summarize recent advancements of these ncRNA mediators in the brain vasculature, highlighting the specific roles of endothelial miRNAs in stroke.
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