在肺高血压引起的右心室功能障碍中,线粒体电子运输链超复合体的活性和丰度的减少
bioRxiv : the preprint server for biology
|July 15, 2024
概括
线粒体超级复合体 (mSC) 在肺高血压 (PH) 诱导的右心室 (RV) 功能障碍中减少. 这种功能障碍与RV代谢受损和PH大鼠和人类ROS生成增加有关.
科学领域:
- 心血管研究研究心血管研究
- 线粒体生物学 线粒体生物学
- 肺高血压的病理生理学
背景情况:
- 肺高血压 (PH) 会导致右心室 (RV) 缩,纤维化和衰竭.
- RV衰竭涉及RV代谢和线粒体呼吸功能受损.
- 线粒体超级复合体 (mSC) 可能增强呼吸并减少ROS生成.
研究的目的:
- 调查线粒体超级复合体 (mSC) 是否在与PH相关的RV功能障碍中减少.
- 评估mSC活动和RV功能障碍标志物之间的相关性.
主要方法:
- 在大鼠中通过Sugen/Hypoxia诱导PH.
- 心声学,蓝色本地PAGE和心肌细胞隔离用于评估mSC丰度,活性和ROS.
- 从具有和没有RV功能障碍的患者获得的人类RV组织的分析.
主要成果:
- 在PH大鼠中,mSC中的RV活性和CI,CIII和CIV的丰度显著降低.
- 隔离的PH RV肌细胞显示线粒体ROS生成增加.
- 在老鼠模型和人类患者中观察到减少的mSC活性和与VR功能障碍标志物 (例如RAP/PCWP) 的相关性.
结论:
- 线粒体mSCs的组装和活性减少与PH中的RV功能障碍有很强的相关性.
- 线粒体功能障碍,特别是受损的mSC功能,是PH相关的RV衰竭的关键特征.
- 针对mSC可能为PH相关的RV功能障碍提供治疗策略.
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