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Published on: December 15, 2023
Chloride Channels - New Targets for the Prevention of Stroke
1Department of Pharmacology, Cardiac & Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan 2 Rd, Guangzhou, 510080, P. R. China. guanyy@mail.sysu.edu.cn.
Insights
Hypertension alters chloride channels in brain blood vessels, increasing stroke risk. Targeting these channels, like volume-regulated Cl(-) channels (VRCC) and calcium-activated Cl- channels (CaCC), may offer new stroke prevention strategies.
Area of Science:
- Neuroscience
- Cardiovascular Biology
- Molecular Physiology
Background:
- Stroke is a major global health concern, with hypertension-induced cerebrovascular remodeling being a key risk factor.
- Cerebral vascular smooth muscle cells (VSMC) utilize volume-regulated Cl(-) channels (VRCC) and calcium-activated Cl- channels (CaCC) for crucial functions.
- Hypertension is associated with altered activity of these chloride channels in VSMC.
Purpose of the Study:
- To review recent findings on the roles of VRCC and CaCC in VSMC during hypertension.
- To explore the involvement of these channels in cellular processes contributing to cerebrovascular remodeling.
- To discuss potential therapeutic targets for stroke prevention related to chloride channels.
Main Methods:
- Review of current scientific literature on chloride channels (ClC-3 and TMEM16A) in VSMC.
- Analysis of studies investigating channel function in the context of hypertension and cerebrovascular remodeling.
- Examination of the relationship between channel activity and stroke prevention agents.
Main Results:
- ClC-3 is identified as a likely VRCC, and TMEM16A as the CaCC in brain VSMC.
- VRCC activity increases, while CaCC activity decreases in cerebral VSMC with escalating hypertension.
- These chloride channels influence VSMC proliferation, apoptosis, inflammation, and oxidative stress.
Conclusions:
- Altered VRCC and CaCC activity in VSMC are implicated in hypertension-related cerebrovascular remodeling and stroke risk.
- Chloride channels represent promising novel therapeutic targets for stroke prevention.
- Further research into VRCC and CaCC modulation could lead to new clinical strategies.
Abstract:
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.
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