GPR146通过PIEZO1促进血压升高和血管重塑
Zhenzhen Chen1, Haizeng Zhang1,2, Wendong Li3
1Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital of Capital Medical University, China (Z.C., H.Z., Q.L., J.C.).
Circulation research
|July 10, 2025
概括
G蛋白结合受体146 (GPR146) 通过激活cAMP-CREB1-PIEZO1通路来驱动高血压和血管重塑. 阻断GPR146为高血压提供了一个有前途的治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 药理学 药理学 是一个学科.
背景情况:
- 高血压是一种全球性健康问题,其特点是水静压升高.
- G蛋白结合受体 (GPCRs) 对于调节血管度至关重要,并代表关键药物标.
- 鉴定参与高血压的特定GPCR对于开发新疗法至关重要.
研究的目的:
- 确定涉及高水静压 (HP) 的关键GPCR.
- 阐明GPR146在高血压和血管改造中的作用和机制.
- 评估GPR146作为高血压的治疗点.
主要方法:
- RNA测序用于在高HP下识别高表达的GPCR.
- 生成GPR146淘汰赛和淘汰赛小鼠模型 (全球和血管光滑肌细胞特异性).
- 外体HP加载系统,体外信号测定和体内治疗性抗体给药.
主要成果:
- 在高HP下,GPR146被确定在血管光滑肌细胞中高度表达.
- GPR146促进血管收缩,表型切换,血压升高和血管重塑.
- GPR146激活cAMP-CREB1信号通路,从而调节PIEZO1的表达,从而调节GPR146的影响.
结论:
- 通过Gαs和cAMP-CREB1-PIEZO1通路,GPR146对高血压和血管重塑作出了显著的贡献.
- GPR146的中和证明了在缓解高血压和血管损伤方面具有治疗潜力.
- 准GPR146为管理高血压提供了一个可行的策略.
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