Polo-like kinase 1 promotes sepsis-induced myocardial dysfunction

Zhenqiang Gao; Cuiting Zheng; Yaqi Xing; Xiyu Zhang; Yunfei Bai; Chen Chen; Yuanyuan Zheng; Wen Wang; Hongbing Zhang; Yan Meng

doi:10.1016/j.intimp.2023.111074

Polo-like kinase 1 promotes sepsis-induced myocardial dysfunction

Int Immunopharmacol. 2023 Dec;125(Pt A):111074. doi: 10.1016/j.intimp.2023.111074. Epub 2023 Oct 23.

Authors

Zhenqiang Gao¹, Cuiting Zheng², Yaqi Xing¹, Xiyu Zhang¹, Yunfei Bai¹, Chen Chen³, Yuanyuan Zheng⁴, Wen Wang⁵, Hongbing Zhang⁶, Yan Meng⁷

Affiliations

¹ Department of Pathology, Beijing Lab for Cardiovascular Precision Medicine, Key Laboratory of Medical Engineering for Cardiovascular Disease, Capital Medical University, Beijing, China.
² Department of Pathology, Beijing Lab for Cardiovascular Precision Medicine, Key Laboratory of Medical Engineering for Cardiovascular Disease, Capital Medical University, Beijing, China; State Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
³ China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Beijing, China.
⁴ Department of Pharmacology, Capital Medical University, Beijing, China.
⁵ Department of Pathology, Beijing Lab for Cardiovascular Precision Medicine, Key Laboratory of Medical Engineering for Cardiovascular Disease, Capital Medical University, Beijing, China; National Demonstration Center for Experimental Basic Medical Education, Capital Medical University, Beijing, China.
⁶ State Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
⁷ Department of Pathology, Beijing Lab for Cardiovascular Precision Medicine, Key Laboratory of Medical Engineering for Cardiovascular Disease, Capital Medical University, Beijing, China. Electronic address: yanmeng_my@ccmu.edu.cn.

PMID: 37879229
DOI: 10.1016/j.intimp.2023.111074

Abstract

Sepsis-induced myocardial dysfunction (SIMD) is the main cause of mortality in sepsis. In this study, we identified Polo-like kinase 1 (Plk-1) is a promoter of SIMD. Plk-1 expression was increased in lipopolysaccharide (LPS)-treated mouse hearts and neonatal rat cardiomyocytes (NRCMs). Inhibition of Plk-1 either by heterozygous deletion of Plk-1 or Plk-1 inhibitor BI 6727 alleviated LPS-induced myocardial injury, inflammation, cardiac dysfunction, and thereby improved the survival of LPS-treated mice. Plk-1 was identified as a kinase of inhibitor of kappa B kinase alpha (IKKα). Plk-1 inhibition impeded NF-κB signal pathway activation in LPS-treated mouse hearts and NRCMs. Augmented Plk-1 is thus essential for the development of SIMD and is a druggable target for SIMD.

Keywords: Lipopolysaccharide; NF-κB; Polo-like kinase 1; Sepsis-induced myocardial dysfunction.

MeSH terms

Animals
Cardiomyopathies* / etiology
Cardiomyopathies* / metabolism
Lipopolysaccharides / pharmacology
Mice
Myocardium / metabolism
NF-kappa B / metabolism
Polo-Like Kinase 1
Rats
Sepsis* / metabolism

Substances

NF-kappa B
Lipopolysaccharides