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Role of AIM2 Gene Knockdown Mechanism in Diabetic Cardiomyopathy: an In Vivo and Ex Vivo Study

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Abstract

Chronic hyperglycemia induces reactive oxygen species that have an essential function in tissue injuries in cases of diabetic cardiomyopathy. The mechanism of the absent in melanoma 2 (AIM2)-associated inflammasome response in diabetic cardiomyopathy is unknown. Therefore, this study was performed to investigate the role of AIM2 and its molecular mechanisms. Diabetic rats received 1 × 108 viral injections of 5′-GGTCACCAGTTCCTCAGTT-3′ (n = 15) or 5′-TTCTCCGAACGTGTCACGT-3′ (negative control group, n = 15). Normal rats (n = 15) and diabetic rats (n = 15) were also included in the experiment. Ex vivo study was performed on primary cardiomyocytes for different concentrations of glucose. AIM2 inhibition did not affect any of the metabolic parameters (p > 0.05 for all). AIM2 protein levels were significantly increased in rats with diabetes mellitus compared with those in the control group (p < 0.0001, q = 32.044). Also, viral injection (sequence: 5′-GGTCACCAGTTCCTCAGTT-3′) decreased the diabetes mellitus-induced increase in expression of AIM2 protein levels (p < 0.0001, q = 27.129). Cardiac dysfunctions were reported in rats with diabetes mellitus characterized by several parameters (p < 0.01 for all). The diabetic myocardium of rats was reported to have higher deposits of extracellular matrix compared to the control rats (p < 0.001). These effects were downregulated by viral injection (sequence: 5′-GGTCACCAGTTCCTCAGTT-3′). Ex vivo research revealed that high glucose concentrations significantly increased AIM2 protein expression, reactive oxygen species, and cell death. AIM2 protein in diabetic cardiomyopathy is associated with reactive oxygen species production and cardiomyocyte death.

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Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

Abbreviations

AIM2:

Absent in melanoma 2

ANOVA:

Analysis of variance

SD:

Standard deviation

Q :

Critical value for post hoc analysis

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Acknowledgements

The authors are thankful to the higher authorities for the facilities provided.

Funding

This work was supported by grants from the Department of Health of Hebei Province (20150148, 1020140269, 20130129).

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Author notes

  1. Qiang Li and Yonghui Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiovascular Surgery, Hebei Chest Hospital, Hebei Lung Cancer Research Center, Shijiazhuang, 050041, Hebei, China

    Qiang Li, Yonghui Liu & Zili Meng

  2. Department of Radiology, Hebei Chest Hospital, Hebei Lung Cancer Research Center, Shijiazhuang, 050041, Hebei, China

    Jiatian Meng

  3. Nursing Department of the Operating Theater, Hebei Chest Hospital, Hebei Lung Cancer Research Center, Shijiazhuang, 050041, Hebei, China

    Xiaoyu Li

  4. Department of Thoracic Surgery, Hebei Chest Hospital, Hebei Lung Cancer Research Center, Shijiazhuang, 050041, Hebei, China

    Hui Li

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  1. Qiang Li
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This study was done by the authors named in this article, and the authors accept all liabilities resulting from claims which relate to this article and its contents.

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Correspondence to Zili Meng.

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Ethics Approval and Consent to Participate

All investigations were conducted in accordance with the National Institutes of Health Guidelines for the Protection and Handling of Laboratory Animals (USA), as approved by the institute’s local ethics board Reg. No: (3276/2020/CPCDIA/12.03.2021), as well as animal care and practice requirements.

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Li, Q., Liu, Y., Meng, J. et al. Role of AIM2 Gene Knockdown Mechanism in Diabetic Cardiomyopathy: an In Vivo and Ex Vivo Study. Appl Biochem Biotechnol 195, 3533–3545 (2023). https://doi.org/10.1007/s12010-022-04306-8

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  • DOI: https://doi.org/10.1007/s12010-022-04306-8

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