肝脏 ангиотензиноген的损失减轻了心力衰竭的扩张功能
Zetao Heng1,2,3,4,5, Min Hong1,2,3,4,5, Zhaocai Zhang6
1Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|September 1, 2025
概括
向肝脏血管新生素 (AGT) 改善了心力衰竭中的心力衰竭. 这项研究显示,
科学领域:
- 心血管研究
- 分子医学
- 脏生理学
背景情况:
- 心脏衰竭与保存的喷射分数 (HFpEF) 是一个复杂的综合征与腹功能障碍和少数治疗.
- 素- 血管素系统 (RAS) 参与心力衰竭,但血管素原 (AGT) 在HFpEF中的具体作用尚不清楚.
研究的目的:
- 研究血管新生素 (AGT) 在心力衰竭 (HFpEF) 的致病作用.
- 探索针对HFpEF肝脏AGT的潜在治疗策略.
主要方法:
- 使用HFpEF (高脂肪饮食+L-NAME) 的双击小鼠模型.
- 评估了肝细胞特异性AGT缺失和系统性血管新素II阻断 (洛萨坦) 的影响.
- 研究了涉及LRP2,GATA2/Pim3信号和微血管血管生成的分子机制.
主要成果:
- 在HFpEF小鼠中观察到肝脏和血AGT的升高.
- 在雄性和雌性HFpEF小鼠中,肝细胞特异性AGT缺失改善了透析功能.
- 系统性洛萨坦没有改善心脏透气功能.
- 发现肝脏AGT通过LRP2介导的内化驱动HFpEF,抑制GATA2/ Pim3信号,抑制血管生成,并恶化腹功能障碍.
- 肝脏AGT抑制剂18β- glycyrrhetinic acid在HFpEF小鼠中显著改善了腹功能.
结论:
- 肝脏AGT是HFpEF发病的一个关键因果因素.
- 针对肝脏AGT是一个有前途的治疗策略.
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