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The miR-214-3p/c-Ski axis modulates endothelial–mesenchymal transition in human coronary artery endothelial cells in vitro and in mice model in vivo

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Abstract

Cardiovascular disease (CVD) is a leading non-communicable disease with a high fatality rate worldwide. Hypertension, a common cardiovascular condition, is a significant risk factor for the development of heart failure because the activation of the renin-angiotensin system (RAS) is considered to be the major promoting reason behind myocardial fibrosis (MF). In this study, Angiotensin II (Ang II) stimulation-induced endothelial to mesenchymal transition (End-MT) in HCAECs, including the decrease of CD31 level, the increase of α-SMA, collagen I, slug, snail, and TGF-β1 levels, and the promotion of Smad2/3 phosphorylation. Meanwhile, the c-Ski level was reduced in Ang II-stimulated HCAECs. In HCAECs, Ang II-induced changes could be partially attenuated by c-Ski overexpression. miR-214-3p directly targeted c-Ski and inhibited c-Ski expression. Moreover, miR-214-3p inhibition reduced Ang II-caused End-MT in HCAECs. miR-214-3p overexpression further enhanced Ang II-induced End-MT, while c-Ski overexpression could markedly reverse the effects of miR-214-3p overexpression. In the Ang II-induced mouse cardiac hypertrophic model, Ang II-caused increase of cellular cross-sectional area and cardiac fibrosis were partially ameliorated by LV-c-Ski; when mice were co-treated with LV-c-Ski and agomir-214-3p, the beneficial effects of LV-c-Ski were reversed. In conclusion, the miR-214-3p/c-Ski axis modulated Ang II-induced End-MT in HCAECs and cardiac hypertrophy and fibrosis in the mice model.

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Acknowledgements

This study was supported by Xinjiang Science and Technology Support Project (2018E02064).

Funding

This study was supported by Xinjiang Science and Technology Support Project (2018E02064).

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Authors and Affiliations

  1. Department of Cardiology, The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, China

    Juan Wang

  2. Department of Hypertension, The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, China

    Hongjian Li, Zhongying Lv, Xiaomei Luo, Ting Zou, Yue Zhang, Wanyue Sang & Xuehua Wang

  3. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China

    Wei Deng

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  1. Juan Wang
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  2. Hongjian Li
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  3. Zhongying Lv
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  4. Xiaomei Luo
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  5. Wei Deng
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  6. Ting Zou
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  7. Yue Zhang
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  9. Xuehua Wang
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Contributions

JW and HL conception and design the experiments. JW drafting the article. HL revising the article critically for important intellectual content. WD contributed to the conception of the study. ZL, XL, TZ and YZ contributed to cell and animal experiments. WS and XW contributed to the analysis and manuscript preparation. All the authors read and approved the manuscript.

Corresponding author

Correspondence to Hongjian Li.

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All authors declare that they have no conflicts of interest in this work.

Ethics approval

All animal experiments were approved by the Animal Ethics Committee of The Fifth Affiliated Hospital of Xinjiang Medical University.

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Fig.S1

The expression of c-Ski, α-SMA, and collagen I in response to the treatment of Ang II of different concentrations (0, 1, 2.5, 5, and 10 μg/ml) for 24 h in HCAECs.. n=3; **P<0.01.Supplementary file 3 (TIF 333 KB)

Fig.S2

The predicted binding site between miR-124-3p and 3'UTR of c-Ski in rat and mouse species. Supplementary file 4 (TIF 203 KB)

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Wang, J., Li, H., Lv, Z. et al. The miR-214-3p/c-Ski axis modulates endothelial–mesenchymal transition in human coronary artery endothelial cells in vitro and in mice model in vivo. Human Cell 35, 486–497 (2022). https://doi.org/10.1007/s13577-021-00653-6

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  • DOI: https://doi.org/10.1007/s13577-021-00653-6

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