Polo-like kinase 1 promotes sepsis-induced myocardial dysfunction.
Int Immunopharmacol
; 125(Pt A): 111074, 2023 Dec.
Article
em En
| MEDLINE
| ID: mdl-37879229
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.
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Base de dados:
MEDLINE
Assunto principal:
Sepse
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Cardiomiopatias
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article