综合多组学揭示了心脏代谢HFpEF中的代谢肌病
bioRxiv : the preprint server for biology
|December 25, 2025
概括
心脏衰竭的骨肌与保存的喷射分数 (HFpEF) 显示严重的线粒体功能障碍和代谢转变. 这项多组学研究揭示了导致HFpEF患者运动不耐受的关键途径.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 生理学 生理学 生理学
背景情况:
- 骨肌肉功能障碍是运动不耐受和心力衰竭中残疾的主要驱动因素,其中包括保留喷射分数 (HFpEF).
- 代谢和线粒体损伤是HFpEF骨肌肉功能障碍的核心.
- 对代谢途径的全面分析对于确定HFpEF运动不耐受症的治疗点至关重要.
研究的目的:
- 在HFpEF中对骨肌进行多组学分析,以阐明失调的代谢途径.
- 为了确定HFpEF中骨肌肉功能障碍背后的特定分子机制.
- 探索提高HFpEF运动能力的潜在治疗目标.
主要方法:
- 使用的雄性ZSF1肥胖大鼠 (HFpEF模型) 和Wistar京都 (WKY) 控制.
- 在胃角肌肌肉上进行了大量的RNA-seq,蛋白质组,代谢组和脂质组.
- 进行了向的血和骨肌肉代谢/脂质组学,分析了肌肉和EDL肌肉.
主要成果:
- 观察到氧化酸化,电子运输链和TCA循环通路的下调.
- 发现了PPAR信号的升级,托代谢和氨基酸氧化途径.
- 发现了TCA中间体的积累,变化的分支链氨基酸 (BCAA) 水平,以及脂物种的变化 (PC,PE增加; arachidonoyl-PC减少).
结论:
- 骨肌的HFpEF表现为严重的线粒体功能障碍 (降低复合I/II活性) 和改变的脂质代谢.
- 不调节的BCAA氧化和托代谢有助于减少阿纳普勒索斯和有毒代谢物积累.
- 研究结果表明,心脏代谢性HFpEF中存在一种获得的代谢性肌肉病变.
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