Chloride Channels - New Targets for the Prevention of Stroke
Chloride Channels - New Targets for the Prevention of Stroke
复制标题
氯离子通道 - 预防中风的新目标
DOI：
10.2174/1570161112666141014145040
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发表时间：
2015-01-01
影响因子：
4.5
通讯作者：
Guan, Yong-Yuan
中科院分区：
文献类型：
--
作者：
Du, Yan-Hua;Guan, Yong-Yuan
中风是世界范围内发病率和死亡率的主要原因。高血压时脑血管重构是脑卒中发生的主要原因之一。容量调节性氯离子通道（VRCC）和钙激活性氯离子通道（CaCC）是脑血管平滑肌细胞（VSMC）中两种主要的氯离子通道。最近的研究表明，ClC-3，电压门控ClC Cl-通道家族的成员，是VSMC中VRCC的分子候选者。TMEM 16 A是Anoctamin家族的成员，负责脑血管中VSMC的天然CaCC。研究表明，高血压引起的脑血管重构的严重程度与脑VSMC中VRCC活性增强而CaCC活性降低相平行。本文就这两个通道在高血压发生发展过程中VSMC增殖、凋亡、细胞周期调控、血管炎症、活性氧产生和脑血管重塑等方面的重要作用作一综述。此外，VRCC与临床使用的预防中风的药物，如他汀类药物之间的关系，将进行讨论。这些发现表明氯离子通道可能是预防脑卒中的潜在新靶点。
Stroke is a leading cause of morbidity and mortality worldwide. It has been generally accepted that cerebrovascular remodeling during hypertension is one of the major contributors to the increased risk of stroke. Volume-regulated Cl- channel (VRCC) and calcium-activated Cl- channel (CaCC) are the two predominant types of Cl- channels in cerebral vascular smooth muscle cells (VSMC). Recent studies have demonstrated that ClC-3, a member of the voltage-gated ClC Cl- channel family, is the molecular candidate for VRCC in VSMC. And TMEM16A, a member of anoctamin family, is responsible for the native CaCC of VSMC in brain vessels. It has been shown that VRCC activity is enhanced but CaCC activity is decreased in cerebral VSMC, paralleling the severity of cerebrovascular remodeling induced by hypertension. In the present review, we will highlight the recent findings regarding the important roles of these two channels in VSMC proliferation, apoptosis, cell cycle regulation, vascular inflammation, reactive oxygen species production and cerebrovascular remodeling during the development of hypertension. In addition, the relationship between VRCC and clinical used agents for stroke prevention, such as statins, will be discussed. These findings suggest that Cl- channels may be potential new targets for the prevention of stroke.