Figure 5.

Signaling pathway diagram. Myocardial ischemia-reperfusion injury (MIRI) increases ROS production, which promotes the association of TXNIP with NLRP3 to activate the inflammasome. Because cardiomyocytes show low levels of the pyroptosis effector protein GSDMD, the apoptotic pathway becomes instead activated due to caspase-1-mediated degradation of the transcription factor GATA4 and consequent downregulation of the anti-apoptotic gene Bcl-2. EVs derived from ADSCs exposed to anoxic preconditioning exert significant cardioprotective effects against MIRI due to a distinct abundance of miRNAs targeting TXNIP. TXNIP downregulation impedes caspase-1 activation and GATA4 degradation, which therefore sustains Bcl-2 expression and prevents MIRI-induced apoptosis of cardiomyocytes.