2. Academic Validation
  3. Cardiac injury activates STING signaling via upregulating SIRT6 in macrophages after myocardial infarction

Cardiac injury activates STING signaling via upregulating SIRT6 in macrophages after myocardial infarction

  • Life Sci. 2024 Mar 15:341:122474. doi: 10.1016/j.lfs.2024.122474.
Weixian Kong 1,  Jiawen Chen 2,  Xinjia Ruan 2,  Xiaozhi Xu 1,  Xie Li 1,  Mengmeng Bao 1,  Yuru Shao 1,  Xiaohong Bian 1,  Ruiyan Li 1,  Qizhou Jiang 1,  Yubin Zhang 1,  Zhe Li 3,  Fangrong Yan 4,  Junmei Ye 5
Affiliations

Affiliations

  • 1 College of Life Science and Technology, China Pharmaceutical University, Nanjing 210006, China.
  • 2 State Key Laboratory of Natural Medicines, Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China.
  • 3 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular research Institute, Wuhan University, Wuhan 430060, China; Hubei key Laboratory of Cardiology, Wuhan 430060, China. Electronic address: [email protected].
  • 4 State Key Laboratory of Natural Medicines, Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China. Electronic address: [email protected].
  • 5 College of Life Science and Technology, China Pharmaceutical University, Nanjing 210006, China. Electronic address: [email protected].
PMID: 38296191 DOI: 10.1016/j.lfs.2024.122474
Abstract

Aims: This work sought to investigate the mechanism underlying the STING signaling pathway during myocardial infarction (MI), and explore the involvement and the role of SIRT6 in the process.

Main methods: Mice underwent the surgery of permanent left anterior descending (LAD) artery constriction. Primary cardiomyocytes (CMs) and fibroblasts were subjected to hypoxia to mimic MI in vitro. STING expression was assessed in the infarct heart, and the effect of STING inhibition on cardiac fibrosis was explored. This study also evaluated the regulatory effect of STING by SIRT6 in macrophages.

Key findings: STING protein was increased in the infarct heart tissue, highlighting its involvement in the post-MI inflammatory response. Hypoxia-induced death of CMs and fibroblasts contributed to the upregulation of STING in macrophages, establishing the involvement of STING in the intercellular signaling during MI. Inhibition of STING resulted in a significant reduction of cardiac fibrosis at day 14 after MI. Additionally, this study identified SIRT6 as a key regulator of STING via influencing its acetylation and ubiquitination in macrophages, providing novel insights into the posttranscriptional modification and expression of STING at the acute phase after myocardial infarction.

Significance: This work shows the key role of SIRT6/STING signaling in the pathogenesis of cardiac injury after MI, suggesting that targeting this regulatory pathway could be a promising strategy to attenuate cardiac fibrosis after MI.

Keywords

Inflammation; Macrophages; Myocardial infarction; SIRT6; STING.

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