title: Cilostazol suppresses angiotensin II-induced apoptosis in endothelial cells.
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.
authors: Department of Pediatrics, Affiliated Bayi Children's Hospital, General Military Hospital of Beijing PLA, Beijing Key Laboratory of Pediatric Organ Failure, Beijing 100700, P.R. China.
authors: Miao-Qian
authors: MQ
authors: Shi
authors: Department of Cardiology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Fei-Fei
authors: FF
authors: Su
authors: Department of Pediatrics, Affiliated Bayi Children's Hospital, General Military Hospital of Beijing PLA, Beijing Key Laboratory of Pediatric Organ Failure, Beijing 100700, P.R. China.
authors: Xuan
authors: X
authors: Xu
authors: Department of Cardiology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Xiong-Tao
authors: XT
authors: Liu
authors: Department of Cardiology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Hong-Tao
authors: HT
authors: Wang
authors: Department of Cardiology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Wei
authors: W
authors: Zhang
authors: Department of Cardiology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Xue
authors: X
authors: Li
authors: Department of Cardiology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Cheng
authors: C
authors: Lian
authors: Department of Cardiology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Qiang-Sun
authors: QS
authors: Zheng
authors: Department of Pediatrics, Affiliated Bayi Children's Hospital, General Military Hospital of Beijing PLA, Beijing Key Laboratory of Pediatric Organ Failure, Beijing 100700, P.R. China.
authors: Zhi-Chun
authors: ZC
authors: Feng
mesh_terms: D000804:Angiotensin II; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D000077407:Cilostazol; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009609:Nitrous Oxide / Q000378:metabolism; D058987:Phosphodiesterase 3 Inhibitors / Q000494:pharmacology*; D051381:Rats; D013481:Superoxides / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D058987:Phosphodiesterase 3 Inhibitors; D013777:Tetrazoles; D013481:Superoxides; D000804:Angiotensin II; D009609:Nitrous Oxide; D000077407:Cilostazol