p16INK4a Aggravated Sepsis-associated Cardiac Injury by Inhibiting the PI3K/AKT Pathway and Inducing Redox Imbalance.

Severe sepsis can promote myocardial injury and cardiac dysfunction, but role of p16 in sepsis-induced myocardial injury remains undefined. PBMCs were collected from patients. Expression of inflammatory factors and NLRP3 pathway were detected by Western blotting and qPCR in WT and p16KO mice. Then detect cardiomyocyte apoptosis and ROS levels in vitro. Detailed pathways and mechanisms were revealed through quantitative proteomic analysis combined with GSEA and KEGG analysis. p16 was overexpressed in PBMCs of patient. p16 knockout alleviated cardiac dysfunction in LPS-induced mice and inhibited NLRP3 inflammasome pathway in vivo and in vitro. Quantitative proteomic analysis revealed that p16 knockout contributed to the activation of the PI3K/Akt pathway in LPS-induced cardiac injury. p16 knockout promoted activation of the PI3K/Akt pathway and ameliorated NLRP3 pathway inhibition and redox imbalance thus improving cardiac function in LPS-induced cardiomyopathy mice.