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Published on: May 21, 2018
AIM2 inflammasome deficiency mitigates cardiac senescence by suppressing GSDMD-executed pyroptosis
Yali Bao1, Gang Wang2, Dina Ainiwaer1
1Department of Pathophysiology, College of Basic Medicine, Xinjiang Medical University, Urumqi, Xinjiang 830000, China.
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.
Insights
AIM2 inflammasome activation drives cardiac senescence and pyroptosis. Inhibiting AIM2 inflammasome may offer strategies to combat cardiomyocyte aging and related cardiovascular diseases.
Area of Science:
- Cardiovascular Research
- Inflammation and Immunity
- Cellular Aging
Background:
- The AIM2 inflammasome is implicated in cardiovascular disease pathology.
- Understanding its role in cardiomyocyte senescence is crucial.
Purpose of the Study:
- To investigate AIM2 inflammasome activation in cardiomyocyte senescence.
- To elucidate the underlying mechanisms involved.
Main Methods:
- Bioinformatics analysis identified senescence-associated pathways.
- In vivo (aged mice) and in vitro (D-galactose treated H9C2 cells) models were used.
- Assessed AIM2, pyroptosis, and senescence markers via molecular and cellular assays.
Main Results:
- Elevated AIM2 expression and inflammasome activation in aged myocardium and senescent cardiomyocytes.
- AIM2 inflammasome activation correlated with increased pyroptosis and senescence markers.
- AIM2 knockdown reduced pyroptosis and senescence in vitro.
Conclusions:
- AIM2 inflammasome activation contributes significantly to cardiac senescence.
- GSDMD-mediated pyroptosis is a key mechanism in AIM2-induced senescence.
- Targeting AIM2 inflammasome may provide therapeutic strategies for cardiomyocyte aging.
