Effects of endothelial progenitor cell-derived microvesicles on hypoxia/reoxygenation-induced endothelial dysfunction and apoptosis.

Effects of endothelial progenitor cell-derived microvesicles on hypoxia/reoxygenation-induced endothelial dysfunction and apoptosis.
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内皮祖细胞来源的微泡对缺氧/复氧诱导的内皮功能障碍和细胞凋亡的影响

DOI:
10.1155/2013/572729
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发表时间:
2013
影响因子:
--
通讯作者:
Chen Y
Chen Y
中科院分区:
生物学2区
文献类型:
--
作者:
Wang J;Chen S;Ma X;Cheng C;Xiao X;Chen J;Liu S;Zhao B;Chen Y

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氧化应激诱导的内皮功能障碍在缺血/再灌注损伤中起关键作用。最近的研究表明,内皮祖细胞衍生的微泡(EPC-MV)可以促进内皮细胞(EC)的血管生成。在这里,我们研究了EPC-MVs对人脑微血管内皮细胞(hb-ECs)缺氧/复氧(H/R)损伤的潜在影响。从在血清剥夺(SD)培养基(饥饿应激,sEPC-MV)或含肿瘤坏死因子-α(TNFα)的SD培养基(凋亡应激,aEPC-MV)中培养的EPC制备MV。用1%O_2低氧6小时复氧24小时的方法建立hb-ECs H/R损伤模型。将H/R hb-EC与EPC-MV共培养。结果表明:(1)H/R hb-ECs功能紊乱,细胞凋亡增加,ROS过量产生;(2)两种不同条件下,EPC-MVs携带caspase 3和miR 126的表达差异显著;(3)sEPC-MVs对H/R hb-ECs功能有促进作用,而aEPC-MVs对H/R hb-ECs有抑制作用;(4)sEPC-MVs和aEPC-MVs的不同作用与miR 126和eNOS表达的变化有关,并可被PI 3 K抑制剂阻断。结论sEPCs-MVs和aEPC-MVs通过其携带的与ROS产生和PI 3 K/eNOS/NO通路相关的RNA在hb-EC凋亡和功能障碍中具有不同的功能。
Oxidative stress-induced endothelial dysfunction plays a key role in ischemia/reperfusion injury. Recent evidence indicates that endothelial progenitor cell-derived microvesicles (EPC-MVs) can promote angiogenesis of endothelial cells (ECs). Here, we investigated the potential effects of EPC-MVs on hypoxia/reoxygenation (H/R) injury in human brain microvascular ECs (hb-ECs). MVs were prepared from EPCs cultured in a serum deprivation (SD) medium (starving stress, sEPC-MVs) or SD medium containing tumor necrosis factor-α (TNFα) (apoptotic stress, aEPC-MVs). H/R injury model of hb-ECs was produced by 6 hr hypoxia (1% O2) and 24 hr reoxygenation. The H/R hb-ECs were co-cultured with EPC-MVs. Results showed that (1) H/R hb-ECs were dysfunctional and coupled with increased apoptosis and ROS overproduction; (2) under two different conditions, EPCs displayed remarkable difference in caspase 3 and miR126 expression, which were carried by the corresponsive EPC-MVs; (3) functionally, sEPC-MVs had beneficial effects on H/R hb-ECs, whereas aEPC-MVs had detrimental effects; (4) the diverse effects of sEPC-MVs and aEPC-MVs were associated with the changes in miR126 and eNOS expression and were abolished by PI3K inhibitor. In conclusion, sEPCs-MVs and aEPC-MVs are functionally different on hb-EC apoptosis and dysfunction via their carried RNAs associated with ROS production and PI3K/eNOS/NO pathway.
DOI: 10.1002/emmm.201202318
发表时间: 2013-07
影响因子: 11.1
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影响因子: 20.3
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影响因子: 6.1
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