Blockade of the Notch Signaling Pathway Promotes M2 Macrophage Polarization to Suppress Cardiac Fibrosis Remodeling in Mice With Myocardial Infarction

Frontiers in Cardiovascular Medicine

Cardiovascular Medicine

Miao Nie¹  Yuanchen He²  Hongguang Han²  Zhi Li²  Dengshun Tao²  Yuji Zhang²  Huishan Wang²  Liming Yu²  Yu Liu²  Qiang Wang² 

[1] College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China;Department of Cardiothoracic Surgery, General Hospital of Northern Theater Command, Shenyang, China;

关键词: Notch signaling pathway;    myocardial infarction;    fibrotic remodeling;    CYLD expression;    macrophage polarization;    inflammation;   

DOI  :  10.3389/fcvm.2021.639476

 received in 2021-01-15, accepted in 2021-11-24,  发布年份 2022

来源: Frontiers

【 摘 要 】

Myocardial infarction (MI) is regarded as a serious ischemic heart disease on a global level. The current study set out to explore the mechanism of the Notch signaling pathway in the regulation of fibrosis remodeling after the occurrence of MI. First, experimental mice were infected with recombination signal binding protein J (RBP-J) shRNA and empty adenovirus vector, followed by the establishment of MI mouse models and detection of cardiac function. After 4 weeks of MI, mice in the sh-RBP-J group were found to exhibit significantly improved cardiac function relative to the sh-NC group. Moreover, knockdown of RBP-J brought about decreased infarct area, promoted cardiac macrophages M2 polarization, reduced cardiac fibrosis, and further decreased transcription and protein expressions of inflammatory factors and fibrosis-related factors. Furthermore, downregulation of cylindromatosis (CYLD) using si-CYLD reversed the results that knockdown of RBP-J inhibited fibrogenesis and the release of inflammatory factors. Altogether, our findings indicated that the blockade of Notch signaling promotes M2 polarization of cardiac macrophages and improves cardiac function by inhibiting the imbalance of fibrotic remodeling after MI.

【 授权许可】

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Copyright © 2022 Li, Nie, Yu, Tao, Wang, He, Liu, Zhang, Han and Wang.