Format

Send to

Choose Destination
Life Sci. 2019 Mar 15;221:249-258. doi: 10.1016/j.lfs.2019.02.035. Epub 2019 Feb 18.

AIM2 gene silencing attenuates diabetic cardiomyopathy in type 2 diabetic rat model.

Author information

1
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China.
2
Department of Cardiology, Shandong Provincial Qianfoshan Hospital of Shandong University, Jinan, Shandong 250012, China.
3
Jinan No. 4 People's Hospital, No. 50, Shifan Road, Jinan, Shandong 250031, China.
4
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China. Electronic address: fengshuang.an@hotmail.com.

Abstract

AIMS:

Absent in melanoma 2 (AIM2) is a cytosolic DNA sensor which plays an important role in inflammasome formation and is involved in various cellular functions including pyroptosis, fibrosis, and tissue injury. Our study aimed to investigate whether AIM2 plays a role in diabetic cardiomyopathy (DCM) and to explore its potential molecular mechanism.

MAIN METHODS:

Sprague-Dawley rats were randomly divided into 4 groups: Control, Diabetes Mellitus (DM), DM + shAIM2, and DM + shNC. The cardiac function of rats was measured. Hematoxylin and eosin staining, Masson's staining, sinus red staining, and immunohistochemistry were performed. H9c2 cardiomyocytes were cultured in DMEM and stimulated with high-glucose treatment (25 mmol/l). The level of reactive oxygen species (ROS) was measured. AIM2-siRNA were used to inhibit the expression of AIM2. TUNEL assay and EthD-III staining were used to measure cell death. The expression levels of AIM2, ASC, caspase-1, IL-1β, and GSDMD-N were measured by western blotting.

KEY FINDINGS:

In the streptozotocin-induced diabetic rat model, AIM2 expression was significantly increased in heart tissue compared with the control. Also, diabetic rats exhibited severe left ventricular dysfunction including metabolic disorder, cardiac fibrosis, and cardiomyocyte death. Gene silencing of AIM2 alleviated cardiac dysfunction which resulted from metabolic disorder and ventricular remodelling. In vitro, treatment of H9C2 cardiomyoblasts with HG significantly increased AIM2, while ROS inhibition reduced the level of AIM2. AIM2-siRNA alleviated GSDMD-N-related pyroptosis in H9c2 cardiomyoblasts.

SIGNIFICANCE:

Our results indicate that AIM2 plays an important role in cell death and fibrosis in HG-induced, ROS-mediated diabetic cardiomyopathy via the GSDMD pathway.

KEYWORDS:

AIM2; Cell death; Diabetic cardiomyopathy; GSDMD; ROS

PMID:
30790610
DOI:
10.1016/j.lfs.2019.02.035
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center