IFN-γ/JAK2/STAT1 Pathway in CAD: AIM2 Inflammasome Activation

June, 06, 2024 | Melanoma, Skin Cancer


  • The study aimed to investigate the mechanism of AIM2 upregulation and its role in inflammasome-induced inflammation in aortic plaques of CAD.
  • Researchers observed that IFN-γ/JAK2/STAT1-induced AIM2 expression promotes monocyte inflammation and pyroptosis, contributing to CAD development.

Numerous studies have demonstrated that Absent in Melanoma 2 (AIM2) is upregulated in aortic plaques, especially in vascular smooth muscle cells in coronary artery disease (CAD), and is related to inflammasome-induced inflammation. However, the underlying mechanism of this phenomenon and the role of AIM2 in atherosclerosis remained unclear.

Yue Zhao and the team aimed to elucidate the mechanism by which AIM2 is upregulated and its specific role in inflammasome-mediated inflammation within aortic plaques associated with CAD.

They performed an inclusive analysis involving 133 patients with CAD and 123 controls. Peripheral Blood Leukocytes (PBLs) were isolated to assess AIM2 inflammasome and downstream gene (ASC, Caspase-1, IL-1β, IL-18) mRNA expression via real-time quantitative PCR (qPCR). Correlations between AIM2 expressions and clinical characteristics were evaluated using multiple linear regression and Spearman’s correlation.

THP-1 cells were cultured under conditions including poly(dA), A151, interferon-gamma (IFN-γ), AG490, or JC2-11. mRNA and protein levels of AIM2, ASC, Caspase-1, IL-1β, IL-18, GSDMD, and STAT1 were analyzed using qPCR and Western blot analysis. Migration and adhesive capacity of THP-1 cells were assessed using inverted and fluorescence microscopes, respectively.

They found that expressions of components of AIM2 inflammasome and its downstream genes (ASC, Caspase-1, IL-1β, and IL-18) were all increased in PBLs of patients with CAD, indicating inflammasome activation. AIM2 inflammasome activation further induced pyroptosis, and stimulated migration and adhesion in monocyte cell lines, which was regulated by IFN-γ probably through JAK2/STAT1 pathway. In addition, AIM2 expressions were positively correlated with systemic inflammatory indicators as an independent risk factor for CAD.

The study concluded that increased AIM2 expression, induced by the IFN-γ/JAK2/STAT1 signal, directs monocytes to an inflammatory status or pyroptosis through AIM2 inflammasome activation, contributing to the development of CAD.

This study was funded by the National Natural Science Foundation of China, Zhongnan Hospital of Wuhan University Joint Fund for Translational Medicine and Interdisciplinary Research International cooperation project of Key Research and Development Program of Hubei Province, and Translation Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University.


Zhao Y, Liang B, Sheng S, et al. (2024). “AIM2 inflammasome regulated by the IFN-γ/JAK2/STAT1 pathway promotes activation and pyroptosis of monocytes in Coronary Artery Disease.” Immun Inflamm Dis. 2024 Jun;12(6):e1317. doi: 10.1002/iid3.1317. PMID: 38869352; PMCID: PMC11170685.

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