Role of toll-like receptor-mediated pyroptosis in sepsis-induced cardiomyopathy

Abstract

Sepsis, a life-threatening dysregulated status of the host response to infection, can cause multiorgan dysfunction and mortality. Sepsis places a heavy burden on the cardiovascular system due to the pathological imbalance of hyperinflammation and immune suppression. Myocardial injury and cardiac dysfunction caused by the aberrant host responses to pathogens can lead to cardiomyopathy, one of the most critical complications of sepsis. However, many questions about the specific mechanisms and characteristics of this complication remain to be answered. The causes of sepsis-induced cardiac dysfunction include abnormal cardiac perfusion, myocardial inhibitory substances, autonomic dysfunction, mitochondrial dysfunction, and calcium homeostasis dysregulation. The fight between the host and pathogens acts as the trigger for sepsis-induced cardiomyopathy. Pyroptosis, a form of programmed cell death, plays a critical role in the progress of sepsis. Toll-like receptors (TLRs) act as pattern recognition receptors and participate in innate immune pathways that recognize damage-associated molecular patterns as well as pathogen-associated molecular patterns to mediate pyroptosis. Notably, pyroptosis is tightly associated with cardiac dysfunction in sepsis and septic shock. In line with these observations, induction of TLR-mediated pyroptosis may be a promising therapeutic approach to treat sepsis-induced cardiomyopathy. This review focuses on the potential roles of TLR-mediated pyroptosis in sepsis-induced cardiomyopathy, to shed light on this promising therapeutic approach, thus helping to prevent and control septic shock caused by cardiovascular disorders and improve the prognosis of sepsis patients.

Keywords: Cardiac dysfunction; Pyroptosis; Sepsis; TLRs.