AIM2炎症小体缺失通过抑制GSDMD介导的焦亡缓解心肌衰老的机制研究

Abstract

Background The AIM2 inflammasome is known to mediate pathological processes in various cardiovascular diseases. This study aims to investigate whether AIM2 inflammasome activation contributes to cardiomyocyte senescence and to explore the underlying mechanisms. Methods Bioinformatics analysis was employed to identify pathways associated with cardiomyocyte senescence. Male BALB/c mice were divided into young and old groups. An in vitro model of cardiomyocyte senescence was established by treating H9C2 cells with D-galactose (D-gal). Expression levels of AIM2, ASC, caspase-1, GSDMD, P53, and P21 were assessed using RT-qPCR, Western blot, ELISA and immunofluorescence. Cell viability was measured by CCK-8 assay, senescence was evaluated by SA-β-gal staining, apoptosis was detected via TUNEL staining and LDH release assay, reactive oxygen species (ROS) levels were determined using the DCFH-DA assay. Results Bioinformatics analysis of a public dataset revealed elevated AIM2 expression in the ventricular tissue of aged mice. This finding was further validated in both in vivo and in vitro models of myocardial senescence. In aging mouse myocardium and D-gal-induced senescent cardiomyocytes, AIM2 inflammasome activation was enhanced, accompanied by increased levels of pyroptosis. Knockdown of AIM2 suppressed D-gal-induced activation of the AIM2 inflammasome and reduced the expression of pyroptosis and senescence markers in cardiomyocytes. Conclusion These findings indicate that AIM2 inflammasome activation plays a critical role in the development of cardiac senescence, in part through GSDMD-mediated pyroptosis. This study provides new insights into potential strategies for preventing or alleviating cardiomyocyte aging.