在肺高血压中,CircALMS1可以缓解肺微血管内皮细胞功能障碍
Xiaoyi Hu1, Yuanyuan Sun2, Shang Wang1
1Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine Tongji University Shanghai China.
循环RNA阿尔斯特罗姆综合征蛋白1 (circALMS1) 在肺高血压 (PH) 和缺氧中降低,影响肺微血管内皮细胞 (PMEC) 功能. 恢复circALMS1水平可能为PH提供治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 分子生物学分子生物学
- 在RNA生物学,RNA生物学.
背景情况:
- 循环RNAs (circRNAs) 与肺高血压 (PH) 的病原发生有关.
- 肺血管内脏损伤中circRNAs的作用尚不清楚.
- 这项研究在低氧和PH条件下研究肺微血管内皮细胞 (PMEC) 中的circRNAs.
研究的目的:
- 在低氧和PH下,在PMEC中特定表达的circRNAs的识别.
- 阐明circALMS1在PH发育和进展中的作用.
- 探索circALMS1对PMEC功能障碍的影响背后的分子机制.
主要方法:
- 深度RNA测序和定量实时PCR用于识别和量化circRNAs.
- 分子生物学技术和组织病理学,以评估PMEC功能和血管改造.
- 在体内研究使用PH的老鼠模型 (单克罗他林和苏根/低氧).
- 在体外实验涉及circALMS1过度表达和淘汰,miRNA分析和目标基因验证 (露西法酶试验).
主要成果:
- 在低氧PMEC和PH患者的血中,circALMS1的表达显著降低,与死亡风险相关.
- 在PH大鼠模型中,circALMS1的过度表达改善了心脏功能,并减少了肺血管重塑.
- circALMS1抑制了PMEC的扩散和迁移,同时通过降低调节miR-17-3p来促进缺氧下的亡,该调节的目标是YTHDF2.2.
- 一个m6A读者YTHDF2在低氧PMEC中被下调,其调节影响了PMEC的功能.
结论:
- circALMS1在与PH相关的PMEC功能障碍中起着保护作用.
- miR-17-3p/YTHDF2通路是circALMS1在缺氧诱导的PMEC功能障碍中的作用的关键调解者.
- circALMS1代表了PH的潜在治疗标,为其致病性提供了洞察力.
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