Cilostazol suppresses angiotensin II-induced apoptosis in endothelial cells.
Mol Med Rep
; 13(3): 2597-605, 2016 Mar.
Article
en En
| MEDLINE
| ID: mdl-26862035
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 caspase3 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 angIIinduced apoptosis of HUVECs; however, this effect was reduced in the presence of LY294002, a phosphoinositide 3 kinase (PI3K) inhibitor. Furthermore, cilostazol suppressed the angIIinduced pAkt downregulation and cleaved caspase3 upregulation. These effects were also alleviated by LY294002. In vivo, cilostazol suppressed the angIIinduced endothelial cell apoptosis and dysfunction. Cilostazol was also demonstrated to partially reduced the angIIinduced increase in superoxide production. The results of the present study suggested that cilostazol suppresses endothelial apoptosis and dysfunction by modulating the PI3K/Akt pathway.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tetrazoles
/
Angiotensina II
/
Apoptosis
/
Inhibidores de Fosfodiesterasa 3
/
Células Endoteliales de la Vena Umbilical Humana
Límite:
Animals
Idioma:
En
Revista:
Mol Med Rep
Año:
2016
Tipo del documento:
Article