在实验性肺高血压中,TRPV2抑制可以防止右心室重塑和心律失常
Zhuonan Song1, Tianxin Ye1, Yunping Zhou1
1Department of Cardiology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
概括
暂时的受体潜在化物2型 (TRPV2) 抑制可以防止肺动脉高血压 (PAH) 诱导的右心室重塑和恶性心律失常. 准TRPV2为与PAH相关的腹腔动提供了一个潜在的治疗策略.
科学领域:
- 心血管研究研究心血管研究
- 分子生物学分子生物学
- 生理学 生理学 生理学
背景情况:
- 肺动脉高血压 (PAH) 的特点是右心室 (RV) 衰竭和恶性心律失常,显著影响预后.
- 在PAH引起的心脏功能障碍和心律失常中,暂时受体潜在化物2型 (TRPV2) 的作用仍然在很大程度上未被探索.
- 了解TRPV2的贡献对于开发PAH新型治疗干预措施至关重要.
研究的目的:
- 调查TRPV2在心室重塑和心律失常的发展中的作用,通过SU5416/hypoxia (SuHx) 诱导的肺动脉高血压 (PAH) 的大鼠模型.
- 阐明TRPV2影响心脏病理和PAH电生理异常的潜在机制.
- 评估TRPV2抑制在缓解PAH相关的RV功能障碍和恶性心律失常的治疗潜力.
主要方法:
- 建立一个由SuHx诱导的PAH大鼠模型.
- 血液动力学测量,心电图和心室电生理学研究.
- 组织学分析 (WGA,H&E,马森三色),免疫光学,qPCR和西部斑点测试以评估结构和分子变化.
- 在体外研究中使用低氧诱导的H9c2细胞与TRPV2或β-catenin小干扰RNA (siRNA).
- 使用tranilast进行TRPV2的药理抑制.
主要成果:
- 在SuHx大鼠中,用tranilast抑制TRPV2显著降低了肺动脉压和血管重塑.
- 抑制TRPV2改善了VR重塑,纤维化,高,并抑制了恶性心律不整,包括心室动 (VF).
- 抑制TRPV2恢复了平衡,减弱了离子通道和连接素重塑,预防了自主功能障碍,并减少了炎症.
- 在体外,TRPV2抑制改善了离子通道重塑,并抑制了IGF1介导的Wnt/β-catenin信号通路.
结论:
- 在肺动脉高血压的背景下,TRPV2在调解右心室重塑和心律失常方面发挥着重要作用.
- 抑制TRPV2显示出对PAH诱导的心脏病理和电气不稳定性的保护作用.
- TRPV2成为预防和治疗与PAH相关的恶性心律不整的有前途的治疗标.
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