Role of caspase-1 and AIM2 inflammasome in ischemia/reperfusion injury of myocardium

Acute myocardial infarction induces a sterile inflammatory response, leading to cardiomyocyte damage and adverse cardiac remodeling. The contribution of inflammasomes has been involved to the cardiac remodeling, however, little is known about its potential role in cardiac hypoxia, especially the AIM2 inflammasome. Thus, the present study aimed to investigate the impact of AIM2-inflammasome absence in the myocardial susceptibility to ischemia/reperfusion (I/R) injury. For this purpose, 3-month-old male mice knockout mice for caspase-1 ( casp-/-) or AIM2 ( aim2 -/-) were used (n=5). Cardiac injury was induced in isolated heart using the ex vivo Langendorff perfusion model (20 minutes of global ischemia and 45 minutes of reperfusion). All protocols were approved by the Ethics Committee on Animal Experimentation of ICB-USP (n05402181121). Casp-/- and aim2 -/- mice showed no significant differences in heart weight to tibia length ratio when compared to wild-type mice ( WT). Supporting these results, the cardiomyocyte area, evaluated on histological slides stained with WGA (wheat germ agglutinin), was similar in all groups. In relation to functional data, post-ischemic recovery of cardiac function was similar between aim2 -/- and WT mice. However, casp-/- mice showed worse recovery after I/R, as evidenced by decreased left ventricular developed pressure (LVDP) (mmHg) and increased resistance in ventricular relaxation (TAU index). In conclusion, we provide evidences that caspase-1 is involved in myocardial susceptibility to ischemia/reperfusion (I/R) injury. Additional experiments are being conducted to increase the number of animals and to evaluate other parameters as cardiomyocyte death. FAPESP (grants number: 2019/17031-2 and 2022/0084-0). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.