The role of TREM-1 in septic myocardial pyroptosis and septic cardiomyopathy in vitro and in vivo

Septic cardiomyopathy (SCM) is an acute cardiac dysfunction involving myocardial cell pyroptosis. TREM-1 is a known receptor on cell membrane that can amplify the inflammatory response. Our previous studies have shown that TREM-1 in cardiomyocytes is involved in the activation of NLRP3 through the SMC4/NEMO pathway. Here, we aimed to use Trem-1 and Nlrp3 knockout mice to verify the effect of TREM-1 through NLRP3 on cardiac function in septic mice. The results showed that TREM-1 knockout resulted in a decrease in the release of downstream cell signals, including SMC4 and NLRP3, resulting in a decrease in cytokine release and improvement of cardiac dysfunction. Knockout of NLRP3 also reduced cardiomyocyte pyroptosis and increased survival rate. The therapeutic targeting of TREM-1 activation of NLRP3 and its pathway may contribute to the treatment or prevention of SCM. TREM-1 activated NlLRP3 through the SMC4/NEMO signaling pathway to promote the progression of septic cardiomyopathy through TREM-1 and SMC4 interaction. The inhibition of TREM-1reduced myocardial injury, improve cardiac function and prolonged the survival of sepsis mice. image