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

• Published in: Journal of cellular physiology 2024-12, Vol.239 (12), p.e31445-n/a
• Main Authors: Chen, Yongxia, Mao, Lixia, Liu, Songtao, Huang, Shunyi, Lin, Qiuyun, Zeng, Man, Huang, Huiyi, Sun, Xiaocong, Chen, Hongpeng, Huang, Jiahao, Zhou, Gaosheng, Deng, Liehua
• Format: Article
• Language: English
• Subjects: Animals; Cardiomyocytes; Cardiomyopathies - genetics; Cardiomyopathies - metabolism; Cardiomyopathies - pathology; Cardiomyopathy; Cell activation; Cell membranes; Cytokines - metabolism; Disease Models, Animal; Heart rate; In vivo methods and tests; Inflammasomes - metabolism; Inflammation; Inflammatory response; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium - metabolism; Myocardium - pathology; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3; Pyroptosis; Sepsis - genetics; Sepsis - metabolism; Sepsis - pathology; septic cardiomyopathy; Signal Transduction; SMC4; Therapeutic targets; TREM‐1; Triggering Receptor Expressed on Myeloid Cells-1 - genetics; Triggering Receptor Expressed on Myeloid Cells-1 - metabolism
• ISSN: 0021-9541; 1097-4652; 1097-4652
• DOI: 10.1002/jcp.31445

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.