炎症性巨噬细胞白细胞介素-1β介导射血分数保留的高脂饮食诱导的心力衰竭。

Inflammatory Macrophage Interleukin-1β Mediates High-Fat Diet-Induced Heart Failure With Preserved Ejection Fraction.

作者信息

Liu Hong, Huang Yimao, Zhao Yang, Kang Gyeoung-Jin, Feng Feng, Wang Xiaodan, Liu Man, Shi Guangbin, Revelo Xavier, Bernlohr David, Dudley Samuel C

机构信息

Division of Cardiology, Department of Medicine, the Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota, USA.

Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.

出版信息

JACC Basic Transl Sci. 2022 Nov 30;8(2):174-185. doi: 10.1016/j.jacbts.2022.08.003. eCollection 2023 Feb.

Diabetes mellitus (DM) is a main risk factor for diastolic dysfunction (DD) and heart failure with preserved ejection fraction. High-fat diet (HFD) mice presented with diabetes mellitus, DD, higher cardiac interleukin (IL)-1β levels, and proinflammatory cardiac macrophage accumulation. DD was significantly ameliorated by suppressing IL-1β signaling or depleting macrophages. Mice with macrophages unable to adopt a proinflammatory phenotype were low in cardiac IL-1β levels and were resistant to HFD-induced DD. IL-1β enhanced mitochondrial reactive oxygen species (mitoROS) in cardiomyocytes, and scavenging mitoROS improved HFD-induced DD. In conclusion, macrophage-mediated inflammation contributed to HFD-associated DD through IL-1β and mitoROS production.

糖尿病（DM）是舒张功能障碍（DD）和射血分数保留的心力衰竭的主要危险因素。高脂饮食（HFD）小鼠出现糖尿病、舒张功能障碍、心脏白细胞介素（IL）-1β水平升高以及促炎性心脏巨噬细胞积聚。通过抑制IL-1β信号传导或清除巨噬细胞，舒张功能障碍得到显著改善。巨噬细胞无法采用促炎表型的小鼠心脏IL-1β水平较低，并且对高脂饮食诱导的舒张功能障碍具有抗性。IL-1β增强了心肌细胞中的线粒体活性氧（mitoROS），清除mitoROS改善了高脂饮食诱导的舒张功能障碍。总之，巨噬细胞介导的炎症通过IL-1β和mitoROS的产生导致了与高脂饮食相关的舒张功能障碍。