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Melatonin attenuates low shear stress‑induced pyroptosis and endothelial cell dysfunction via the RORα/miR‑223/STAT‑3 signalling pathway

  • Authors:
    • Sui Yi
    • Yang Yang
  • View Affiliations / Copyright

    Affiliations: The Intensive Care Unit Department, Second Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China, The Neurology Department, Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, P.R. China
    Copyright: © Yi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 1392
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    Published online on: September 30, 2021
       https://doi.org/10.3892/etm.2021.10828
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Abstract

Endothelial cells sense changes in blood flow shear stress and affect the progression of atherosclerotic plaques. Pyroptosis is an inflammatory form of cell death and has been implicated in cardiovascular diseases. Melatonin and its nuclear receptor retinoid‑related orphan receptor α (RORα) have protective effects on the development of atherosclerosis. To date, whether melatonin can prevent endothelial cell pyroptosis and dysfunction in pathological shear stress remains unclear. In the present study, human umbilical vein endothelial cells (ECs) were cultured under low shear stress conditions (5 dyne/cm2) for 24 h and treated with or without melatonin (2 µmol/l). The binding sites of the microRNA (miR)‑223 promoter and RORα were predicted using the JASPAR website. Expression of pyroptosis‑related proteins, including cleaved N‑terminal gasdermin D, caspase‑1, intercellular adhesion molecule 1 (ICAM‑1) and nitric oxide (NO) were assessed. The results indicated that low shear stress increased pyroptosis and ICAM‑1 expression, whereas it decreased NO levels. Melatonin alleviated pyroptosis and ICAM‑1 expression and increased the production of NO in ECs. Further assessment revealed that low‑level shear stress decreased RORα protein and mRNA expression, whereas melatonin would bind to RORα and thereby promoted miR‑223 transcription in ECs. The present study also identified signal transducer and activator of transcription 3 (STAT‑3) as a potential target gene of miR‑223‑3p. When transfected with miR‑223 inhibitor, ECs up‑regulated the expression of pyroptosis‑related proteins and ICAM‑1, and down‑regulated NO levels. By contrast, silencing STAT‑3 expression diminished the protective effect of miR‑223. These results indicated that melatonin prevented ECs from undergoing pyroptosis and alleviated dysfunction via the RORα/miR‑223/STAT‑3 signalling pathway. This information could aid in the development of novel therapeutic approaches and provide new insights into atherosclerosis.
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Copy and paste a formatted citation
Spandidos Publications style
Yi S and Yang Y: Melatonin attenuates low shear stress‑induced pyroptosis and endothelial cell dysfunction via the RORα/miR‑223/STAT‑3 signalling pathway. Exp Ther Med 22: 1392, 2021.
APA
Yi, S., & Yang, Y. (2021). Melatonin attenuates low shear stress‑induced pyroptosis and endothelial cell dysfunction via the RORα/miR‑223/STAT‑3 signalling pathway. Experimental and Therapeutic Medicine, 22, 1392. https://doi.org/10.3892/etm.2021.10828
MLA
Yi, S., Yang, Y."Melatonin attenuates low shear stress‑induced pyroptosis and endothelial cell dysfunction via the RORα/miR‑223/STAT‑3 signalling pathway". Experimental and Therapeutic Medicine 22.6 (2021): 1392.
Chicago
Yi, S., Yang, Y."Melatonin attenuates low shear stress‑induced pyroptosis and endothelial cell dysfunction via the RORα/miR‑223/STAT‑3 signalling pathway". Experimental and Therapeutic Medicine 22, no. 6 (2021): 1392. https://doi.org/10.3892/etm.2021.10828
Copy and paste a formatted citation
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Spandidos Publications style
Yi S and Yang Y: Melatonin attenuates low shear stress‑induced pyroptosis and endothelial cell dysfunction via the RORα/miR‑223/STAT‑3 signalling pathway. Exp Ther Med 22: 1392, 2021.
APA
Yi, S., & Yang, Y. (2021). Melatonin attenuates low shear stress‑induced pyroptosis and endothelial cell dysfunction via the RORα/miR‑223/STAT‑3 signalling pathway. Experimental and Therapeutic Medicine, 22, 1392. https://doi.org/10.3892/etm.2021.10828
MLA
Yi, S., Yang, Y."Melatonin attenuates low shear stress‑induced pyroptosis and endothelial cell dysfunction via the RORα/miR‑223/STAT‑3 signalling pathway". Experimental and Therapeutic Medicine 22.6 (2021): 1392.
Chicago
Yi, S., Yang, Y."Melatonin attenuates low shear stress‑induced pyroptosis and endothelial cell dysfunction via the RORα/miR‑223/STAT‑3 signalling pathway". Experimental and Therapeutic Medicine 22, no. 6 (2021): 1392. https://doi.org/10.3892/etm.2021.10828
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