Open Access

Cilostazol suppresses angiotensin II‑induced apoptosis in endothelial cells

  • Authors:
    • Miao‑Qian Shi
    • Fei‑Fei Su
    • Xuan Xu
    • Xiong‑Tao Liu
    • Hong‑Tao Wang
    • Wei Zhang
    • Xue Li
    • Cheng Lian
    • Qiang‑Sun Zheng
    • Zhi‑Chun Feng
  • View Affiliations

  • Published online on: February 5, 2016     https://doi.org/10.3892/mmr.2016.4881
  • Pages: 2597-2605
  • Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Patients with essential hypertension undergo endothelial dysfunction, particularly in the conduit arteries. Cilostazol, a type III phosphodiesterase inhibitor, serves a role in the inhibition of platelet aggregation and it is widely used in the treatment of peripheral vascular diseases. Previous studies have suggested that cilostazol suppresses endothelial dysfunction; however, it remains unknown whether cilostazol protects the endothelial function in essential hypertension. The aim of the present study was to investigate whether, and how, cilostazol suppresses angiotensin II (angII)‑induced endothelial dysfunction. Human umbilical vein endothelial cells (HUVECs) and Sprague Dawley rats were exposed to angII and treated with cilostazol. Endothelial cell apoptosis and function, nitric oxide and superoxide production, phosphorylation (p) of Akt, and caspase‑3 protein expression levels were investigated. AngII exposure resulted in the apoptosis of endothelial cells in vitro and in vivo. In vitro, cilostazol significantly suppressed the angII‑induced apoptosis of HUVECs; however, this effect was reduced in the presence of LY294002, a phosphoinositide 3 kinase (PI3K) inhibitor. Furthermore, cilostazol suppressed the angII‑induced p‑Akt downregulation and cleaved caspase‑3 upregulation. These effects were also alleviated by LY294002. In vivo, cilostazol suppressed the angII‑induced endothelial cell apoptosis and dysfunction. Cilostazol was also demonstrated to partially reduced the angII‑induced increase in superoxide production. The results of the present study suggested that cilostazol suppresses endothelial apoptosis and dysfunction by modulating the PI3K/Akt pathway.
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March-2016
Volume 13 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Shi MQ, Su FF, Xu X, Liu XT, Wang HT, Zhang W, Li X, Lian C, Zheng QS, Feng ZC, Feng ZC, et al: Cilostazol suppresses angiotensin II‑induced apoptosis in endothelial cells. Mol Med Rep 13: 2597-2605, 2016
APA
Shi, M., Su, F., Xu, X., Liu, X., Wang, H., Zhang, W. ... Feng, Z. (2016). Cilostazol suppresses angiotensin II‑induced apoptosis in endothelial cells. Molecular Medicine Reports, 13, 2597-2605. https://doi.org/10.3892/mmr.2016.4881
MLA
Shi, M., Su, F., Xu, X., Liu, X., Wang, H., Zhang, W., Li, X., Lian, C., Zheng, Q., Feng, Z."Cilostazol suppresses angiotensin II‑induced apoptosis in endothelial cells". Molecular Medicine Reports 13.3 (2016): 2597-2605.
Chicago
Shi, M., Su, F., Xu, X., Liu, X., Wang, H., Zhang, W., Li, X., Lian, C., Zheng, Q., Feng, Z."Cilostazol suppresses angiotensin II‑induced apoptosis in endothelial cells". Molecular Medicine Reports 13, no. 3 (2016): 2597-2605. https://doi.org/10.3892/mmr.2016.4881