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Full Length Article | Open Access

Mitophagy deficiency activates stimulator of interferon genes activation and aggravates pathogenetic cardiac remodeling

Guoxiang Zhoua,1Xiaowen Wangb,1Mingyu Guoa,1Can QucLei GaoaJiang YuaYuanjing LiaSuxin LuoaQiong Shid( )Yongzheng Guoa( )
Division of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
The Department of Laboratory Medicine, M.O.E. Key Laboratory of Laboratory Medical Diagnostics, Chongqing Medical University, Chongqing 400016, China

1 Those authors contribute equally to this work.

Peer review under responsibility of Chongqing Medical University.

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Abstract

Stimulator of interferon genes (STING) has recently been found to play a crucial role in cardiac sterile inflammation and dysfunction. The role of stimulator of interferon genes (STING) in cardiac sterile inflammation and dysfunction has been recently discovered. This study aims to examine the involvement of STING in pathological cardiac remodeling and the mechanisms that govern the activation of the STING pathway. To investigate this, transverse aortic constriction (TAC) was performed on STING knockout mice to induce pressure overload-induced cardiac remodeling. Subsequently, cardiac function, remodeling, and inflammation levels were evaluated. The STING pathway was found to be activated in the pressure overload-stressed heart and angiotensin Ⅱ (Ang Ⅱ)-stimulated cardiac fibroblasts. Loss of STING expression led to a significant reduction in inflammatory responses, mitochondrial fragmentation, and oxidative stress in the heart, resulting in attenuated cardiac remodeling and dysfunction. Furthermore, the exacerbation of pressure overload-induced STING-mediated inflammation and pathological cardiac remodeling was observed when mitophagy was suppressed through the silencing of Parkin, an E3 ubiquitin ligase. Taken together, these findings indicate that STING represents a newly identified and significant molecule implicated in the process of pathological cardiac remodeling and that mitophagy is an upstream mechanism that regulates STING activation. Targeting STING may therefore provide a novel therapeutic strategy for pathological cardiac remodeling and heart failure.

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Genes & Diseases
Article number: 101074
Cite this article:
Zhou G, Wang X, Guo M, et al. Mitophagy deficiency activates stimulator of interferon genes activation and aggravates pathogenetic cardiac remodeling. Genes & Diseases, 2024, 11(6): 101074. https://doi.org/10.1016/j.gendis.2023.08.003

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Received: 29 March 2023
Revised: 11 July 2023
Accepted: 04 August 2023
Published: 02 September 2023
© 2023 The Authors.

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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