Expression and significance of melanoma deficiency factor 2 in cardiac senescence model

Background Cardiac aging is one of the major causes of the increased prevalence of cardiovascular disease in the elderly. Therefore, it is crucial to understand the pathogenesis of cardiac aging and to identify new therapeutic targets for cardiovascular disease in the elderly.

Objective  To investigate the role of melanoma deficiency factor 2 (AIM2) inflammasome in myocardial senescence model.

Methods Bioinformatics was used to analyze the difference of AIM2 expression in the ventricles of young and old mice. In animal experiment, male BALB/C mice were divided into young (2 months of age) and old (14 months of age) groups according to age, and AIM2, Apoptosis-associated speck-like protein containing a CARD (ASC), Cysteinyl aspartate specific proteinase-1 (Caspase-1) at the protein and mRNA levels were tested in mice of the two groups. At the cellular level, H9C2 cardiomyocytes were treated with different concentrations of (0, 10, 20, 50 g/L) D-gal to prepare cardiomyocyte senescence model, and the cell viability was detected by CCK8 method to determine the optimum D-gal concentration. H9C2 cells were treated with the optimal concentration of D-gal, and the cells were divided into control group and aging group. β-galactosidase staining was used to detect the degree of cell senescence. Western blot, immunofluorescence and RT-qPCR were used to detect the expression of AIM2, ASC and Caspase-1 in cardiomyocytes.

Results The results of bioinformatics showed that the expression level of AIM2 in ventricular myocardium of aged mice was higher than that of young mice (P<0.05). In the animal experiment, the protein and mRNA levels of AIM2, ASC, Caspase-1 in the ventricles of the aged group were higher than those of the young group. The cell viability was determined by CCK8 method, and Cardiomyocyte senescence model was established by D-gal treatment of H9C2 with 20g/L. The protein and mRNA levels of AIM2, ASC and Caspase-1 in the aging group were higher than those in the control group (P<0.05).

Conclusion The results of bioinformatics, in vivo and in vitro experiments show that the protein and mRNA levels of AIM2 inflammasome increase during myocardial senescence, and AI AIM2 inflammasome may play a certain role in the occurrence and development of myocardial senescence, which provides new ideas for the study of the mechanism of cardiac aging.