Gut microbiota aggravate cardiac ischemia-reperfusion injury via regulating the formation of neutrophils extracellular traps

Aims: Myocardial infarction (MI) is a leading cause of death worldwide for which there is no cure. Percutaneous coronary intervention (PCI) can restore blood supply in a timely manner, which greatly reduces the mortality of patients, but ischemia/reperfusion (I/R) injury is inevitable. A number of clinical studies have shown that gut microbiota play an essential role in cardiovascular diseases. This study aims to explore the mechanism of gut microbiota to limit I/R injury.Materials and methods: This study adopted the myocardial I/R model using gut microbiota clearance mice, neutrophil clearance mice and double-scavenging mice, and explored the relationship between gut microbiota and NETs during I/R injury. Neutrophils were isolated in vitro to explore the effect of NETs on myocardial cell injury and its molecular mechanism.Key findings: Gut microbiota aggravate cardiac I/R injury via regulating the formation of NETs. The migration of gut microbiota to blood stimulated the formation of NETs after cardiac I/R. NETs, which can directly lead to apoptosis of myocardial cells and myocardial microvascular endothelial cells. The time point of NETs formation in tissue and blood after I/R were determined by experiments. Significance: It was confirmed that gut microbiota participates in cardiac I/R injury by regulating the formation of NETs, which reveals a new mechanism of I/R injury and provides a new potential target for the treatment of I/R injury.