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Exogenous hydrogen sulfide reduces atrial remodeling and atrial fibrillation induced by diabetes mellitus via activation of the PI3K/Akt/eNOS pathway

  • Authors:
    • Xiaofei Xue
    • Xinyu Ling
    • Wang Xi
    • Pei Wang
    • Jianjun Sun
    • Qian Yang
    • Jian Xiao
  • View Affiliations / Copyright

    Affiliations: Center for Comprehensive Treatment of Atrial Fibrillation, Department of Cardiothoracic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China, Department of Rehabilitation, Elderly Rehabilitation Hospital, Suzhou Red Cross Society, Suzhou, Jiangsu 215009, P.R. China
    Copyright: © Xue et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1759-1766
    |
    Published online on: June 30, 2020
       https://doi.org/10.3892/mmr.2020.11291
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Abstract

Diabetes mellitus (DM) facilitates atrial fibrosis and increases the risk of atrial fibrillation (AF). The underlying mechanism of DM in causing AF remains mostly unknown and potential therapeutic targets for DM‑induced AF are rarely reported. Hydrogen sulfide (H2S) has drawn considerable attention in recent years for its potential as a cardiovascular protector. Thus, the aim of the present study was to investigate the effect of H2S on DM‑induced AF and the mechanism of action. Sprague‑Dawley rats were divided into four groups, including the control group, the DM group, the H2S group and the DM+H2S group. The DM group and the DM+H2S group were administered streptozotocin to induce DM, whereas the other two groups were given citrate buffer as a control. The H2S group and the DM+H2S group were administered with an intraperitoneal injection of sodium hydrosulfide (precursor of H2S). AF inducibility, AF duration, atrial fibrosis and vital protein expression of oxidative stress were compared among the four groups. The DM group showed significantly higher AF incidence rates and duration (P<0.05). Histology results demonstrated severe atrial fibrosis in the DM group, and the PI3K/Akt/endothelial nitric oxide synthase (eNOS) pathway was significantly downregulated (P<0.05). However, when H2S was administered, the rats showed lower AF incidence and duration compared with the DM group. Additionally, H2S was able to mitigate the atrial fibrosis induced by DM, as well as the proliferation and migration of cardiac fibroblasts, as demonstrated by an MTT assay and real‑time cell analyzer migration experiment. Western blotting showed that the expression levels of the PI3K/Akt/eNOS pathway in the DM+H2S group were significantly upregulated compared with those of the DM group (P<0.05). In summary, DM status can lead to the structural remodeling of atrial fibrosis, facilitating AF incidence and persistence. Administration of H2S does not affect the glucose level, but can significantly mitigate atrial fibrosis and reduce the incidence of AF induced by DM, probably via activation of the PI3K/Akt/eNOS pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Xue X, Ling X, Xi W, Wang P, Sun J, Yang Q and Xiao J: Exogenous hydrogen sulfide reduces atrial remodeling and atrial fibrillation induced by diabetes mellitus via activation of the PI3K/Akt/eNOS pathway. Mol Med Rep 22: 1759-1766, 2020.
APA
Xue, X., Ling, X., Xi, W., Wang, P., Sun, J., Yang, Q., & Xiao, J. (2020). Exogenous hydrogen sulfide reduces atrial remodeling and atrial fibrillation induced by diabetes mellitus via activation of the PI3K/Akt/eNOS pathway. Molecular Medicine Reports, 22, 1759-1766. https://doi.org/10.3892/mmr.2020.11291
MLA
Xue, X., Ling, X., Xi, W., Wang, P., Sun, J., Yang, Q., Xiao, J."Exogenous hydrogen sulfide reduces atrial remodeling and atrial fibrillation induced by diabetes mellitus via activation of the PI3K/Akt/eNOS pathway". Molecular Medicine Reports 22.3 (2020): 1759-1766.
Chicago
Xue, X., Ling, X., Xi, W., Wang, P., Sun, J., Yang, Q., Xiao, J."Exogenous hydrogen sulfide reduces atrial remodeling and atrial fibrillation induced by diabetes mellitus via activation of the PI3K/Akt/eNOS pathway". Molecular Medicine Reports 22, no. 3 (2020): 1759-1766. https://doi.org/10.3892/mmr.2020.11291
Copy and paste a formatted citation
x
Spandidos Publications style
Xue X, Ling X, Xi W, Wang P, Sun J, Yang Q and Xiao J: Exogenous hydrogen sulfide reduces atrial remodeling and atrial fibrillation induced by diabetes mellitus via activation of the PI3K/Akt/eNOS pathway. Mol Med Rep 22: 1759-1766, 2020.
APA
Xue, X., Ling, X., Xi, W., Wang, P., Sun, J., Yang, Q., & Xiao, J. (2020). Exogenous hydrogen sulfide reduces atrial remodeling and atrial fibrillation induced by diabetes mellitus via activation of the PI3K/Akt/eNOS pathway. Molecular Medicine Reports, 22, 1759-1766. https://doi.org/10.3892/mmr.2020.11291
MLA
Xue, X., Ling, X., Xi, W., Wang, P., Sun, J., Yang, Q., Xiao, J."Exogenous hydrogen sulfide reduces atrial remodeling and atrial fibrillation induced by diabetes mellitus via activation of the PI3K/Akt/eNOS pathway". Molecular Medicine Reports 22.3 (2020): 1759-1766.
Chicago
Xue, X., Ling, X., Xi, W., Wang, P., Sun, J., Yang, Q., Xiao, J."Exogenous hydrogen sulfide reduces atrial remodeling and atrial fibrillation induced by diabetes mellitus via activation of the PI3K/Akt/eNOS pathway". Molecular Medicine Reports 22, no. 3 (2020): 1759-1766. https://doi.org/10.3892/mmr.2020.11291
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