类他类药物改善心脏内皮功能,通过上调circRNA-RBCK1来预防心力衰竭,并保留排气分数
Bin Li1,2, Wen-Wu Bai1, Tao Guo1
1State Key Laboratory for Innovation and Transformation of Luobing Theory, the Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China.
Nature communications
|April 5, 2024
概括
通过上调AP-2α/circRNA-RBCK1信号传导,他类药物可以预防心力衰竭中心力衰竭的扩张功能障碍,从而保持喷射率 (HFpEF). 这种机制抑制心脏内皮细胞中的microRNA-133a,改善心脏功能.
科学领域:
- 心血管生物学 心血管生物学
- 分子心脏病学分子心脏病学
- 内皮细胞功能 内皮细胞功能
背景情况:
- 保存喷射分数 (HFpEF) 的心力衰竭与内皮功能障碍有关.
- 过去,他类药物通过抑制microRNA-133a (miR-133a) 来预防内皮功能障碍的潜力已经被证明.
研究的目的:
- 调查他类药物对HFpEF的影响.
- 阐明 HFpEF 中他类药物的作用的潜在分子机制.
主要方法:
- 研究了他类药物对内皮细胞中circRNA-RBCK1表达和AP-2α活性的影响.
- 研究了circRNA-RBCK1和miR-133a之间的相互作用.
- 在体内使用HFpEF的小鼠模型来评估洛瓦斯塔丁对扩张功能的影响,包括对内皮AP-2α和circRNA-RBCK1功能丧失的实验.
主要成果:
- 类药物上调循环RNA-RBCK1 (circRNA-RBCK1) 表达,与RBCK1基因共同转录.
- 类他类药物增强了激活蛋白2α (AP-2α) 的转录活性,促进了circRNA-RBCK1与miR-133a的相互作用.
- 在内皮细胞中,AP-2α直接与RBCK1基因促进体结合.
- 洛瓦斯塔丁在HFpEF小鼠中改善了透缩功能,这种效应因内皮AP-2α或circRNA-RBCK1缺乏而被废除.
结论:
- 类他类药物激活心脏内皮细胞中的AP-2α/circRNA-RBCK1通路.
- 这种信号级联抑制了miR-133a,从而防止了HFpEF中的透缩功能障碍.
- 这些发现突出了在HFpEF中通过他类药物介导的心脏保护的新机制.
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