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Article

Cilostazol regulates the expressions of endothelin‑1 and endothelial nitric oxide synthase via activation of the p38 MAPK signaling pathway in HUVECs

  • Authors:
    • Ying Xue
    • Xiaoye Li
    • Zi Wang
    • Qianzhou Lv
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Pharmacy, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
  • Article Number: 77
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    Published online on: July 29, 2022
       https://doi.org/10.3892/br.2022.1560
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Abstract

Cilostazol is a selective inhibitor of phosphodiesterase type III that inhibits platelet aggregation. The beneficial effects of cilostazol have been attributed not only to its antiplatelet functions but also to its actions on the endothelium. Whether cilostazol regulates endothelin‑1 (ET‑1) and endothelial nitric oxide synthase (eNOS) through mitogen‑activated protein kinase (MAPK) remains undetermined. The aim of this study was to investigate the effects of cilostazol on ET‑1 and eNOS expression in HUVECs, and to assess its relationship with MAPK activity. HUVECs were cultured in vitro, stimulated with TNF‑α, and pretreated with different concentrations of cilostazol. ET‑1 and eNOS levels in the supernatant were detected by ELISA. RT‑qPCR was performed to detect the mRNA expression levels of ET‑1 and eNOS. The phosphorylation levels of p38/MAPK and protein expression levels of ET‑1 and eNOS were assessed using western blotting. A P38 inhibitor, SB203580, was utilized to further validate the involvement of p38/MAPK in the regulation. Expression of ET‑1, which was upregulated by TNF‑α, was significantly suppressed by cilostazol in a dose‑dependent manner, meanwhile, with as the cilostazol concentration was increased, the expression of eNOS increased as well. In addition, cilostazol also decreased phosphorylation of p38, which was upregulated by TNF‑α. The observed upregulation of eNOS and ET‑1 levels were completely abolished upon p38 inhibitor treatment, indicating the involvement of the p38/MAPK pathway in cilostazol‑induced regulation of eNOS and ET‑1 in HUVECs. The results indicated that cilostazol regulates ET‑1 and eNOS production by suppressing the p38/MAPK signaling pathway in TNF‑α‑stimulated HUVECs, and this may contribute to the protective effects of cilostazol on the endothelium.
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Copy and paste a formatted citation
Spandidos Publications style
Xue Y, Li X, Wang Z and Lv Q: Cilostazol regulates the expressions of endothelin‑1 and endothelial nitric oxide synthase via activation of the p38 MAPK signaling pathway in HUVECs. Biomed Rep 17: 77, 2022.
APA
Xue, Y., Li, X., Wang, Z., & Lv, Q. (2022). Cilostazol regulates the expressions of endothelin‑1 and endothelial nitric oxide synthase via activation of the p38 MAPK signaling pathway in HUVECs. Biomedical Reports, 17, 77. https://doi.org/10.3892/br.2022.1560
MLA
Xue, Y., Li, X., Wang, Z., Lv, Q."Cilostazol regulates the expressions of endothelin‑1 and endothelial nitric oxide synthase via activation of the p38 MAPK signaling pathway in HUVECs". Biomedical Reports 17.3 (2022): 77.
Chicago
Xue, Y., Li, X., Wang, Z., Lv, Q."Cilostazol regulates the expressions of endothelin‑1 and endothelial nitric oxide synthase via activation of the p38 MAPK signaling pathway in HUVECs". Biomedical Reports 17, no. 3 (2022): 77. https://doi.org/10.3892/br.2022.1560
Copy and paste a formatted citation
x
Spandidos Publications style
Xue Y, Li X, Wang Z and Lv Q: Cilostazol regulates the expressions of endothelin‑1 and endothelial nitric oxide synthase via activation of the p38 MAPK signaling pathway in HUVECs. Biomed Rep 17: 77, 2022.
APA
Xue, Y., Li, X., Wang, Z., & Lv, Q. (2022). Cilostazol regulates the expressions of endothelin‑1 and endothelial nitric oxide synthase via activation of the p38 MAPK signaling pathway in HUVECs. Biomedical Reports, 17, 77. https://doi.org/10.3892/br.2022.1560
MLA
Xue, Y., Li, X., Wang, Z., Lv, Q."Cilostazol regulates the expressions of endothelin‑1 and endothelial nitric oxide synthase via activation of the p38 MAPK signaling pathway in HUVECs". Biomedical Reports 17.3 (2022): 77.
Chicago
Xue, Y., Li, X., Wang, Z., Lv, Q."Cilostazol regulates the expressions of endothelin‑1 and endothelial nitric oxide synthase via activation of the p38 MAPK signaling pathway in HUVECs". Biomedical Reports 17, no. 3 (2022): 77. https://doi.org/10.3892/br.2022.1560
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