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干扰素马信号驱动心脏代谢重新连接

Ebram Tharwat Melika^1,2,3, DiyaaElDin Ashour^1,2, Kyoungmin Kim⁴

¹Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany.

bioRxiv : the preprint server for biology

|September 15, 2025

概括

系统性干扰素- (IFN-γ) 重新编程心脏新陈代谢,增加葡萄糖的使用,减少氧化酸化. 这发生在心肌细胞中通过直接的IFN-γ信号传递,影响衰老和心力衰竭中的心脏功能.

科学领域:

心脏病学心脏病学
免疫学免疫学免疫学
代谢过程中的代谢.

背景情况:

干扰素- (IFN-γ) 信号影响心肌炎症和心力衰竭 (HF) 中的纤维化.
IFN-γ对心肌细胞的直接影响尚不清楚.
开发了一种新的体内模型来研究IFN-γ对心脏代谢和功能的影响.

研究的目的:

研究IFN-γ对心肌细胞代谢和心脏功能的直接影响.
阐明IFN-γ影响心肌神经代谢重编程的机制.
评估心肌细胞IFN-γ受体在调解这些影响中的作用.

主要方法:

亚相关病毒 (AAV) 载体被用于诱导小鼠的肝脏特异性IFN-γ产生.
评估心脏功能和新陈代谢使用心声回声学,体内成像,RNA测序,代谢学和线粒体检测.
用心肌细胞特异缺失IFN-γ受体的小鼠来确定细胞内在影响.

主要成果:

系统性IFN-γ过度表达导致心脏代谢适应,葡萄糖吸收增加,脂肪酸氧化和氧化酸化减少.
RNA测序揭示了IFN-γ反应特征和关键代谢途径的下调.
线粒体功能测试显示氧气消耗减少,代谢学证实向糖解转移.
这些代谢变化在缺乏心肌细胞IFN-γ受体的小鼠中是不存在的.

结论:

系统性IFN-γ通过通过心肌细胞IFNGR的直接信号在心脏中诱导显著的代谢重编程.
这种重编程涉及葡萄糖吸收增加和氧化酸化减少,反映了老化和心力衰竭中的变化.
除了其炎症作用之外,IFN-γ在调节心脏新陈代谢方面发挥着至关重要的作用.

关键词:

在T细胞,T细胞.心脏代谢心脏代谢这是心肌细胞 (cardiomyocytes).干扰剂干扰剂干扰剂干扰剂线粒体中的线粒体.

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