Effect of cellular senescence on the albumin permeability of blood-derived endothelial cells

Effect of cellular senescence on the albumin permeability of blood-derived endothelial cells
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DOI:
10.1152/ajpheart.00182.2012
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发表时间:
2012-12-01
影响因子:
4.8
通讯作者:
Truskey, George A.
Truskey, George A.
中科院分区:
医学2区
文献类型:
--
作者:
Cheung, Tracy M.;Ganatra, Mansi P.;Truskey, George A.

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Cheung TM,Ganatra MP,Peters EB,Truskey GA.细胞衰老对血源性内皮细胞白蛋白通透性的影响。Am J Physiol Heart Circ Physiol 303:H1374-H1383,2012。首次发表于2012年9月28日; doi:10.1152/ajpheart.00182.2012.-在这项研究中,我们测试的假设,即来自人脐带血(hCB-ECs)的内皮细胞(ECs)表现出低渗透性,随着hCB-ECs的年龄和衰老而增加,hCB-ECs的渗透性的变化是由于紧密连接蛋白定位和cAMP(Epac)1激活的交换蛋白的活性的变化。Transwell膜上低传代hCB-EC单层的白蛋白渗透性比人主动脉EC(HAEC)低10倍(P < 0.01),但与动脉中的体内值相似。hCB-ECs紧密连接蛋白occludin的表达及酪氨酸磷酸化水平均低于HAECs(P < 0.05)。hCB-ECs较HAECs有更多的有丝分裂(P < 0.01)。自分离以来经历>44次群体倍增的hCB-EC具有比经历> 44次群体倍增的hCB-EC显著更高的渗透性。
Cheung TM, Ganatra MP, Peters EB, Truskey GA. Effect of cellular senescence on the albumin permeability of blood-derived endothelial cells. Am J Physiol Heart Circ Physiol 303: H1374-H1383, 2012. First published September 28, 2012; doi:10.1152/ajpheart.00182.2012.-In this study, we tested the hypotheses that endothelial cells (ECs) derived from human umbilical cord blood (hCB-ECs) exhibit low permeability, which increases as hCB-ECs age and undergo senescence, and that the change in the permeability of hCB-ECs is due to changes in tight junction protein localization and the activity of exchange protein activated by cAMP (Epac)1. Albumin permeability across low-passage hCB-EC monolayers on Transwell membranes was 10 times lower than for human aortic ECs (HAECs) (P < 0.01) but similar to in vivo values in arteries. Expression of the tight junction protein occludin and tyrosine phosphorylation of occludin were less in hCB-ECs than in HAECs (P < 0.05). More hCB-ECs than HAECs underwent mitosis (P < 0.01). hCB-ECs that underwent >44 population doublings since isolation had a significantly higher permeability than hCB-ECs that underwent