2. Academic Validation
  3. AIM2 inflammasome regulated by the IFN-γ/JAK2/STAT1 pathway promotes activation and pyroptosis of monocytes in Coronary Artery Disease

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.
Yue Zhao 1,  Bin Liang 1 2 3,  Shuyang Sheng 1,  Chen Wang 1,  Bingyu Jin 1,  Xiaokang Zhang 1,  Yating Cheng 1,  Changxin Shen 4,  Fang Zheng 1
Affiliations

Affiliations

  • 1 Center for Gene Diagnosis and Department of Clinical Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 2 Department of Clinical Laboratory, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 3 Key Clinical Laboratory of Henan Province, Zhengzhou, China.
  • 4 Department of Blood Transfusion, Zhongnan Hospital of Wuhan University, Wuhan, China.
PMID: 38869352 DOI: 10.1002/iid3.1317
Abstract

Background: 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.

Methods: This study enrolled 133 CAD patients and 123 controls. We isolated Peripheral Blood Leukocytes (PBLs) and the mRNA expression of AIM2 inflammasome and its downstream genes (ASC, Caspase-1, IL-1β, and IL-18) were detected by real-time quantitative PCR (qPCR). We assessed correlations between AIM2 expressions and clinical characteristics by multiple linear regression and spearman's correlation. The THP-1 cells cultured in poly(dA:dT), A151, interferon-gamma (IFN-γ), AG490, or JC2-11. And then the mRNA and protein levels of AIM2, ASC, Caspase-1, IL-1β, IL-18, GSDMD, and STAT1 were analyzed by qPCR and Western blot analysis, respectively. The migration and adhesive capacity of THP-1 cells was assessed using an inverted microscope and an inverted fluorescence microscope, respectively.

Results: In this study, we 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 CAD patients, which indicated the 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.

Conclusions: In conclusion, increased AIM2 expression, induced by the IFN-γ/JAK2/STAT1 signal, orientates monocytes to inflammatory status or even Pyroptosis through AIM2 inflammasome activation, which is involved in the development of CAD.

Keywords

AIM2; Coronary Artery Disease; IFN‐γ/JAK2/STAT1 pathyway; inflammasome; monocytes; pyroptosis.

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