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AIM2 Deficiency Alleviates Cardiac Inflammation and Hypertrophy in HFD/STZ-Induced Diabetic Mice by Inhibiting the NLRC4/IRF1 Signaling Pathway.
Wu, Jian-Ping; Wu, Cheng; Ma, Yuan-Ji; Zhu, Jian-Bing; Ma, Lei-Lei; Kong, Fei-Juan.
Afiliación
  • Wu JP; Department of Anesthesiology and Pain Medicine, The Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China.
  • Wu C; Department of Anesthesiology and Pain Medicine, The Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China.
  • Ma YJ; Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Yi Xue Yuan Rd, Xu Hui District, Shanghai, 200032, China.
  • Zhu JB; Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Yi Xue Yuan Rd, Xu Hui District, Shanghai, 200032, China.
  • Ma LL; Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Yi Xue Yuan Rd, Xu Hui District, Shanghai, 200032, China. mllsdjn@126.com.
  • Kong FJ; Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Wu Jin Rd, Hong Kou District, Shanghai, 200032, China. kongfeijuan@163.com.
J Cardiovasc Transl Res ; 2024 Sep 04.
Article en En | MEDLINE | ID: mdl-39230659
ABSTRACT
Absent in melanoma 2(AIM2) exacerbates atherosclerosis by inflammasome assembly. However, AIM2-mediated inflammation in diabetic cardiomyopathy remains incompletely understood. Here we investigate the role of AIM2 in high glucose (HG)- and diabetes-induced inflammatory cardiomyopathy. By RNA-seq, we found that AIM2 were significantly upregulated in HG-induced macrophages, upregulation of AIM2 in cardiac infiltrating macrophages was confirmed in a high-fat diet (HFD)/streptozotocin (STZ)-induceddiabetic mouse model . Therefore, AIM2 knockout mice were constructed. Compared to WT mice, HFD/STZ-induced cardiac hypertrophy and dysfunction were significantly improved in AIM2-/- mice, despite no changes in blood glucose and body weight. Further, AIM2 deficiency inhibited cardiac recruitment of M1-macrophages and cytokine production. Mechanistically, AIM2-deficient macrophgaes reduced IL-1ß and TNF-α secretion, which impaired the NLRC4/IRF1 signaling in cardiomyocytes, and reduced further recruitment of macrophages, attenuated cardiac inflammation and hypertrophy, these effects were confirmed by silencing IRF1 in WT mice, and significantly reversed by overexpression of IRF1 in AIM2-/- mice. Taken together, our findings suggest that AIM2 serves as a novel target for the treatment of diabetic cardiomyopathy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Cardiovasc Transl Res Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Cardiovasc Transl Res Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos