Role of inflammasomes and its regulation in the myocardium after ischemia and reperfusion

Purpose: The adverse ventricular remodeling is used to describe a variety of changes in the myocardium following an infarct that comprises the functionality of the heart, and it is associated with a worse clinical outcome. The advance in the knowledge of this process is critical to design new therapeutic agents to prevent or reverse the heart failure associated. Inflammation is an immune response against tissue injury in order to repair the damage. Different immune cells and inflammatory mediators participate in this process and could result in the activation of the multiprotein complex called inflammasome. However, the molecular events underlying this inflammatory response are incompletely understood. The present study aimed to investigate the role of inflammasomes and its regulation in the myocardium after ischemia and reperfusion. Methods: Rats were randomly divided into sham operation and myocardial ischemia/reperfusion (MI/R, 30 min ischemia followed by 90 min reperfusion). Real-time PCR was used to study the relative expression of a panel of genes on demand participating in the inflammasome complex. Results: The ischemic heart exhibited enhanced inflammasome activation showing a significant upregulation of Nlrp3 and Il1b expression. Moreover, significant upregulations in Cd14, Nod2 and Txnip expression suggested that different pathways may mediate activation of the Nlrp3 inflammasome in the ischemic and reperfused heart. Conclusion: Interventions that block Txnip/Nlrp3, Cd14/Txnip or Nod2/Nlrp3 signalling seem to be candidate target for strategies to prevent the inflammatory response associated to adverse ventricular remodelling induced by MI/R injury.