Frontiers in Pharmacology (Jul 2021)
Il12a Deletion Aggravates Sepsis-Induced Cardiac Dysfunction by Regulating Macrophage Polarization
- Zhen Wang,
- Zhen Wang,
- Zhen Wang,
- Menglin Liu,
- Di Ye,
- Di Ye,
- Di Ye,
- Jing Ye,
- Jing Ye,
- Jing Ye,
- Menglong Wang,
- Menglong Wang,
- Menglong Wang,
- Jianfang Liu,
- Jianfang Liu,
- Jianfang Liu,
- Yao Xu,
- Yao Xu,
- Yao Xu,
- Jishou Zhang,
- Jishou Zhang,
- Jishou Zhang,
- Mengmeng Zhao,
- Mengmeng Zhao,
- Mengmeng Zhao,
- Yongqi Feng,
- Yongqi Feng,
- Yongqi Feng,
- Shuwan Xu,
- Shuwan Xu,
- Shuwan Xu,
- Wei Pan,
- Wei Pan,
- Wei Pan,
- Zhen Luo,
- Zhen Luo,
- Zhen Luo,
- Dan Li,
- Jun Wan,
- Jun Wan,
- Jun Wan
Affiliations
- Zhen Wang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Zhen Wang
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Zhen Wang
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Menglin Liu
- Department of Emergency, Renmin Hospital of Wuhan University, Wuhan, China
- Di Ye
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Di Ye
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Di Ye
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Jing Ye
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Jing Ye
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Jing Ye
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Menglong Wang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Menglong Wang
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Menglong Wang
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Jianfang Liu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Jianfang Liu
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Jianfang Liu
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Yao Xu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Yao Xu
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Yao Xu
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Jishou Zhang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Jishou Zhang
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Jishou Zhang
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Mengmeng Zhao
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Mengmeng Zhao
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Mengmeng Zhao
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Yongqi Feng
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Yongqi Feng
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Yongqi Feng
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Shuwan Xu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Shuwan Xu
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Shuwan Xu
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Wei Pan
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Wei Pan
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Wei Pan
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Zhen Luo
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Zhen Luo
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Zhen Luo
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Dan Li
- Department of Pediatrics, Renmin Hospital of Wuhan University, Wuhan 430060, China
- Jun Wan
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Jun Wan
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Jun Wan
- Hubei Key Laboratory of Cardiology, Wuhan, China
- DOI
- https://doi.org/10.3389/fphar.2021.632912
- Journal volume & issue
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Vol. 12
Abstract
Cardiac dysfunction is a well-recognized complication of sepsis and is associated with the outcome and prognosis of septic patients. Evidence suggests that Il12a participates in the regulation of various cardiovascular diseases, including heart failure, hypertension and acute myocardial infarction. However, the effects of Il12a in sepsis-induced cardiac dysfunction remain unknown. In our study, lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) model were used to mimic sepsis, and cardiac Il12a expression was assessed. In addition, Il12a knockout mice were used to detect the role of Il12a in sepsis-related cardiac dysfunction. We observed for the first time that Il12a expression is upregulated in mice after LPS treatment and macrophages were the main sources of Il12a. In addition, our findings demonstrated that Il12a deletion aggravates LPS-induced cardiac dysfunction and injury, as evidenced by the increased serum and cardiac levels of lactate dehydrogenase (LDH) and cardiac creatine kinase-myocardial band (CK-MB). Moreover, Il12a deletion enhances LPS-induced macrophage accumulation and drives macrophages toward the M1 phenotype in LPS-treated mice. Il12a deletion also downregulated the activity of AMP-activated protein kinase (AMPK) but increased the phosphorylation levels of p65 (p-p65) and NF-κB inhibitor alpha (p-IκBα). In addition, Il12a deletion aggravates CLP-induced cardiac dysfunction and injury. Treatment with the AMPK activator AICAR abolishes the deterioration effect of Il12a deletion on LPS-induced cardiac dysfunction. In conclusion, Il12a deletion aggravated LPS-induced cardiac dysfunction and injury by exacerbating the imbalance of M1 and M2 macrophages. Our data provide evidence that Il12a may represent an attractive target for sepsis-induced cardiac dysfunction.
Keywords