The effects of DPP-4 inhibitor on hypoxia-induced apoptosis in human umbilical vein endothelial cells
The effects of DPP-4 inhibitor on hypoxia-induced apoptosis in human umbilical vein endothelial cells
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DOI：
10.1016/j.jphs.2016.12.003
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发表时间：
2017-01-01
影响因子：
3.5
通讯作者：
Takano, Hiroyuki
中科院分区：
文献类型：
--
作者：
Nagamine, Akari;Hasegawa, Hiroshi;Takano, Hiroyuki
二肽基肽酶-4 （DPP-4）抑制剂是一类用于2型糖尿病患者的新型口服降糖药，具有潜在的抗动脉粥样硬化特性。同时，DPP-4抑制剂对动脉粥样硬化的保护作用机制尚不清楚。我们的目的是确定DPP-4抑制剂对培养内皮细胞的作用及其机制。缺氧条件下培养人脐静脉内皮细胞（HUVECs）。为评价DPP-4抑制剂对HUVECs的保护作用，在细胞培养基中加入DPP-4抑制剂，采用TUNEL法测定细胞活力。我们研究了与DPP-4抑制剂作用有关的细胞内信号通路。抑制DPP-4通过抑制缺氧条件下HUVECs的凋亡而发挥有益作用。DPP-4抑制剂的抗凋亡作用通过CXCR4拮抗剂或Stat3抑制剂预处理而被消除。DPP-4抑制通过抑制缺氧条件下HUVECs的凋亡而对HUVECs产生有益作用。SDF-1 α /CXCR4/Stat3通路可能参与DPP-4抑制剂的细胞保护作用机制。这些结果表明，DPP-4抑制剂具有保护血管的潜力。(C) 2017年作者。由Elsevier b.v.代表日本药理学会制作和主持。这是一篇基于CC BY-NC-ND许可（http://creativecommons.org/licenses/by-nc-nd/4.0/）的开放获取文章。
Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of oral hypoglycemic agents for patients with type 2 diabetes mellitus and have potential antiatherosclerotic properties. Meanwhile, it is unclear how DPP-4 inhibitors have protective effects on atherosclerosis. Our aim was to determine the effects and its mechanisms of DPP-4 inhibitors on cultured endothelial cells. Human umbilical vein endothelial cells (HUVECs) were cultured in hypoxic condition. To evaluate the protective effects of DPP-4 inhibitor on HUVECs, DPP-4 inhibitor was added in the cell culture medium and the cell viability was assessed by TUNEL assay. And we examined the intracellular signaling pathways in relation to the effects of DPP-4 inhibitor. DPP-4 inhibition had beneficial effects by inhibiting the apoptosis under hypoxic conditions in HUVECs. The antiapoptotic effects of DPP-4 inhibitor were abolished by the pretreatment with a CXCR4 antagonist or a Stat3 inhibitor. DPP-4 inhibition has beneficial effects on HUVECs by inhibiting the apoptosis under hypoxic conditions. SDF-1 alpha/CXCR4/Stat3 pathways might be involved in the mechanisms of the cytoprotective effects of DPP-4 inhibitor. These results suggested that DPP-4 inhibitor has a potential for protecting vessels. (C) 2017 The Authors. Production and hosting by Elsevier B. V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).