Polo-like kinase 1 promotes sepsis-induced myocardial dysfunction

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 (IKK alpha). Plk-1 inhibition impeded NF-xB 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.

Automated summary

In sepsis, Plk-1 promotes the development of SIMD. Inhibition of Plk-1 improves LPS-induced myocardial injury and inflammation, and enhances the survival rate of mice. Plk-1 inhibition also impedes NF-κB signal pathway activation.