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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/30949


    標題: Activation of endothelial NO synthase by a xanthine derivative ameliorates hypoxia-induced apoptosis in endothelial progenitor cells
    作者: Wu, Jiunn-Ren
    Hsu, Jong-Hau
    Dai, Zen-Kong
    Wu, Bin-Nan
    Chen, Ing-Jun
    Liou, Shu-Fen
    Yeh, Jwu-Lai
    貢獻者: Kaohsiung Med Univ, Dept Pediat, Kaohsiung Med Univ Hosp
    Kaohsiung Med Univ, Dept Paediat, Fac Med, Coll Med
    Kaohsiung Med Univ, Grad Inst Med, Coll Med
    Kaohsiung Med Univ, Dept & Grad Inst Pharmacol, Fac Med, Coll Med
    Chia Nan Univ Pharm & Sci, Dept Pharm
    Natl Sun Yat Sen Univ, Dept Marine Biotechnol & Resources
    關鍵字: apoptosis
    endothelial nitric oxide synthase
    endothelial progenitor cells
    hypoxia
    kmup-1
    日期: 2016-06
    上傳時間: 2018-01-18 11:38:32 (UTC+8)
    出版者: Wiley
    摘要: Objectives Endothelial damage is strongly associated with cardiovascular diseases such as atherosclerosis, thrombosis and hypertension. Endothelial progenitor cells (EPCs) are primitive bone marrow (BM) cells that possess the capacity to mature into endothelial cells and play a role in neovascularization and vascular remodelling. This study aimed to investigate whether KMUP-1, a synthetic xanthine-based derivative, atorvastatin and simvastatin, can prevent endothelial dysfunction and apoptosis induced by hypoxia and to elucidate the underlying mechanisms. Methods Mononuclear cells were separated and were induced to differentiate into EPCs. KMUP-1, atorvastatin or simvastatin were administered prior to hypoxia. Key findings We found that EPCs exposed to hypoxia increased apoptosis as well as diminished proliferation. Pretreatment with KMUP-1, atorvastatin and simvastatin significantly prevented hypoxia-induced EPCs death and apoptosis, with associated increased of the Bcl-2/Bax ratio, and reduced caspase-3 and caspase-9 expression. We also assessed the nitrite production and Ser(1177)-phospho-eNOS expression and found that KMUP-1, atorvastatin and simvastatin not only increased the secretion of NO compared with the hypoxia group but also upregulated the eNOS activation. Conclusions KMUP-1 inhibited hypoxia-induced dysfunction and apoptosis in EPCs, which may be mediated through suppressing oxidative stress, upregulating eNOS and downregulating the caspase-3 signalling pathway.
    關聯: Journal of Pharmacy and Pharmacology, v.68 n.6, pp.810-818
    Appears in Collections:[藥學系(所)] 期刊論文

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