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内皮FIS1脱SUMOylation可以防止低毒性肺高血压
Xiaofei Zhou1,2, Yuanqing Jiang1,2, Yuewen Wang3
1Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province of Sir Run Run Shaw Hospital (X. Zhou, Y.J., L.F., Yunhui Zhu, Y.C., Yiran Wang, Yingyi Zhu, X. Zhu, R.R., D.L., C.Q., L.Y.), Hangzhou, China.
Circulation research
|August 17, 2023
概括
肺内皮线粒体中FIS1蛋白的脱SUMOylation通过在缺氧压力下保持线粒体完整性和功能来保护肺内皮线粒体免受高血压 (PH). 这一过程对于适应缺氧和防止PH发展至关重要.
科学领域:
- 心血管生物学 心血管生物学
- 线粒体生物学 线粒体生物学
- 肺高血压的发病因子 肺高血压的发病因子
背景情况:
- 肺高血压 (PH) 是一种血管重塑性疾病,死亡率高,通常由缺氧驱动.
- 肺动脉对PH中缺氧压力的反应的精确机制仍然不完全理解.
- 内皮线粒体在感知氧气张力方面发挥着关键作用,SUMOylation (小型泛素类修饰剂修饰) 与缺氧相关的血管病变有关.
研究的目的:
- 阐明SUMOylation在缺氧诱导的肺高血压期间在内皮线粒体中的作用.
- 研究肺动脉内皮细胞对低氧压力的反应机制.
- 确定与缺氧相关的PH的潜在治疗点.
主要方法:
- 使用慢性缺氧小鼠和苏根/缺氧大鼠模型来治疗PH.
- 通过电子和免疫光显微镜评估线粒体形态和结构.
- 量化了线粒体代谢 (氧气消耗,细胞外酸化) 和蛋白质相互作用 (免疫沉).
主要成果:
- 在内皮线粒体中FIS1的SENP1介导的脱SUMOylation在PH标本中被确定并在体外验证.
- 短期缺氧促进SENP1转位,促进FIS1脱SUMOylation,MFN2寡合化,并保持线粒体完整性和ER-线粒体通信.
- 长时间的缺氧会通过miR-138损害FIS1脱SUMOylation,导致线粒体功能障碍和代谢变化,加剧PH表型.
结论:
- 在内皮线粒体内FIS1的脱SUMOylation是一种自适应机制,可以保护内皮功能免受低氧压力,从而防止PH.
- 在肺内皮中FIS1脱SUMOylation和SUMOylation之间的过渡是缺氧PH的内在病原性过程.
- 准FIS1脱SUMOylation是一个潜在的治疗策略,用于管理缺氧PH.
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