大动脉光滑肌TRPV4通道调节高盐诱导高血压的血管收缩
Xin Wen1, Yidi Peng2, Yuefeng Peng1
1Wuxi School of Medicine, Jiangnan University, Wuxi, 214000, China.
概括
在血管光滑肌肉驱动高血压中的过渡受体潜在化物4 (TRPV4) 通道. 高盐饮食通过增加平滑肌肉中的,IP3R2和IRF7信号增强TRPV4诱导的收缩.
科学领域:
- 心血管生理学心血管生理学
- 分子生物学分子生物学
- 高血压研究 高血压研究
背景情况:
- 血管内皮暂时受体潜在化物4 (TRPV4) 通道与高血压有关.
- 在高血压期间血管光滑肌肉中TRPV4通道的作用在很大程度上是未知的.
- 高盐饮食 (HSD) 是高血压的重要危险因素.
研究的目的:
- 在高盐饮食引起的高血压期间研究血管光滑肌肉中TRPV4通道的功能.
- 阐明TRPV4介导的高血压中平滑肌肉收缩所涉及的信号通路.
主要方法:
- 在孤立的小鼠大动脉上进行了线路肌肉学实验.
- 细胞内 ([Ca2+]i) 度和Ca2+成像分析.
- RNA测序 (RNA-seq) 和西方斑点分析.
- 药理上抑制内醇三酸盐受体 (IP3Rs) 的作用.
主要成果:
- TRPV4通道激活诱导大动脉光滑肌收缩,这些收缩在HSD小鼠中得到增强.
- TRPV4激活导致HSD小鼠的大动脉光滑肌细胞 (ASMC) 中[Ca2+]i显著增加.
- 伊诺西三酸盐受体2 (IP3R2) 表达和活性在HSD小鼠的ASMC中增加,调解TRPV4诱导的收缩.
- 全转录组分析发现干扰素调节因子7 (IRF7) 是TRPV4-IRF7-IP3R2信号通路中的一个关键组成部分.
结论:
- 血管光滑肌中的TRPV4通道在高盐饮食引起的高血压中起着至关重要的作用.
- 在高血压中,TRPV4-IRF7-IP3R2信号轴有助于增加[Ca2+]i和平滑肌肉收缩.
- 准TRPV4通道或相关的信号分子可能为高血压提供治疗策略.
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