Affiliation:
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
Abstract
AbstractBackgroundNumerous 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.MethodsThis 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.ResultsIn 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.ConclusionsIn 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.
Funder
National Natural Science Foundation of China