减轻内质网膜压力作为肺高血压治疗的新治疗策略
Peter Dromparis1, Roxane Paulin, Trevor H Stenson
1Department of Medicine Cardiology, University of Alberta, Edmonton, AB, Canada T6G 2B7.
像4-甲酸 (PBA) 这样的化学伴随剂可以通过减少内分泌网膜 (ER) 压力来治疗肺动脉高血压. 这种新的方法针对ER压力来改善肺动脉功能并逆转疾病的进展.
科学领域:
- 心血管研究研究心血管研究
- 细胞生物学 细胞生物学
- 分子医学是分子医学.
背景情况:
- 细胞内膜网膜 (ER) 压力与肺动脉高血压 (PAH) 病原发生有关.
- ER压力有助于肺动脉壁重塑,扩散和PAH中的亡抵抗.
- 在PAH中ER应激的治疗向尚未先前被探索.
研究的目的:
- 研究化学伴侣在减轻ER压力和治疗肺动脉高血压方面的治疗潜力.
- 为了确定化学伴侣是否可以抑制ER-线粒体破坏,并逆转PAH相关的细胞变化.
主要方法:
- 使用小鼠和老鼠的肺高血压模型 (低氧和单类).
- 使用的化学伴侣物是4-甲基酸 (PBA) 和tauroursodeoxycholic酸.
- 评估了肺血液动力学,血管改造,右心室缩,ER压力标志物,线粒体功能和细胞增殖/细胞亡.
主要成果:
- 在小鼠中,PBA治疗可以预防和逆转慢性缺氧诱导的肺高血压,改善血液动力学和减少重塑.
- 化学陪伴剂改善了ER压力,减少了激活转录因子6的激活,并改善了线粒体功能.
- PBA和tauroursodeoxycholic酸抑制了肺动脉平滑肌肉细胞的增殖和诱导的细胞亡在体外和体内.
结论:
- 使用临床上可用的化学伴侣来减轻ER压力代表了肺高血压的一种有前途的新疗法策略.
- 这种方法证明了治疗肺动脉高血压患者的高转化潜力.
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