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综合系统生物学确定了线粒体功能和新陈代谢的破坏是HFpEF的关键贡献者

Andrew A Gibb¹, Kyle LaPenna², Ryan B Gaspar³

¹Center for Cardiometabolic Science, Christina Lee Brown Envirome Institute, Department of Medicine, University of Louisville, Louisville, Kentuck, USA; Aging and Cardiovascular Discovery Center, Department of Cardiovascular Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, USA.

JACC. Basic to translational science

|August 16, 2025

概括

保存喷射分数 (HFpEF) 的心力衰竭涉及代谢和转录的变化. 这项对肥胖大鼠的研究强调了线粒体能量代谢和炎症受损是HFpEF病理学的关键驱动因素.

科学领域:

心血管生物学心血管生物学
代谢学代谢学代谢学
系统生物学系统生物学

背景情况:

保存喷射分数 (HFpEF) 的心力衰竭影响大约50%的心力衰竭病例.
ZSF1肥胖大鼠模型表现出关键的HFpEF特征,如高血压,肥胖和腹功能障碍.
了解HFpEF机制需要区分高血压的影响与同时发生的代谢综合征.

研究的目的:

通过系统生物学方法阐明HFpEF的代谢和转录特征.
在ZSF1肥胖大鼠模型中确定有助于HFpEF发展的机制性途径.
为了区分单独由高血压驱动的分子变化与高血压与代谢综合征相结合.

主要方法:

14周后ZSF1-肥胖,ZSF1-瘦高血压和WKY对照大鼠的生理表型.
左心室 (LV) 组织的无偏置代谢和RNA测序.
分析线粒体形态,功能和心肌细胞超结构.

主要成果:

单独高血压 (ZSF1-lean vs. WKY) 显示了新陈代谢重塑,增加了葡萄糖分解和改变了 purin/pyrimidine 代谢.
ZSF1肥胖大鼠表现出恶化的代谢重塑,显著的转录性变化 (炎症上升,线粒体功能下降) 和减少的能量状态.
综合的奥米克揭示了线粒体功能受损,ATP生产减少,线粒体大小/晶状体密度减少,以及HFpEF心脏中的脂质滴增加.

结论:

在ZSF1-肥胖老鼠模型中集成的奥米克为理解HFpEF病原体提供了一个框架.
线粒体能量代谢功能障碍是HFpEF的一个关键因素.
识别新的途径和点,特别是在线粒体代谢中,对于未来的HFpEF干预至关重要.

关键词:

HFpEF HFpEF 的意思是什么意思进行心脏重塑.心脏衰竭是因为心脏衰竭.代谢代谢代谢代谢线粒体中的线粒体.

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