Chronic hypoxia impairs extracellular nucleotide metabolism and barrier function in pulmonary artery vasa vasorum endothelial cells.
Chronic hypoxia impairs extracellular nucleotide metabolism and barrier function in pulmonary artery vasa vasorum endothelial cells.
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DOI：
10.1007/s10456-011-9234-0
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发表时间：
2011-12
期刊：
影响因子：
9.8
通讯作者：
Gerasimovskaya, Evgenia V.
中科院分区：
文献类型：
--
作者：
Yegutkin, Gennady G.;Helenius, Mikko;Kaczmarek, Elzbieta;Burns, Nana;Jalkanen, Sirpa;Stenmark, Kurt;Gerasimovskaya, Evgenia V.
血管重塑在以缺氧和炎症为显著特征的多种病理生理条件下起着关键作用。血管内ATP、ADP和腺苷被认为是血管张力、渗透性和稳态的重要调节剂，然而嘌呤能信号对内皮细胞生长和血管生成的贡献仍然知之甚少。本研究采用新生犊牛肺动脉外膜血管内皮细胞（vasa vasorum endothelial cells，VVEC），观察缺氧对新生犊牛肺动脉血管生成部位微血管内皮网络生化和功能特性的影响。与常氧对照组相比，缺氧动物的VVEC的特征是：（1）三磷酸核苷二磷酸水解酶-1（nucleotide triphosphate diphosphate-phosphohydrolase-1）NTPDase-1/CD 39和外5′-核苷酸酶/CD 73的活性均随细胞外ATP和ADP水平的升高而升高。（2）低微摩尔浓度的ATP和ADP可引起较高的增殖反应;和（3）血管屏障功能的增强的渗透性和紊乱的腺苷能控制（测量为70 kDa异硫氰酸荧光素-葡聚糖的细胞旁通量）。总之，这些结果表明，独特的模式嘌呤介导的血管生成激活和增强泄漏的VVEC从慢性缺氧血管可能是由紊乱的内皮细胞核苷酸稳态活性新血管形成的网站。
Vascular remodeling plays a pivotal role in a variety of pathophysiological conditions where hypoxia and inflammation are prominent features. Intravascular ATP, ADP and adenosine are known as important regulators of vascular tone, permeability and homeostasis, however contribution of purinergic signalling to endothelial cell growth and angiogenesis remains poorly understood. By using vasa vasorum endothelial cells (VVEC) isolated from pulmonary artery adventitia of control and chronically hypoxic neonatal calves, these studies were aimed to evaluate the effect of hypoxia on biochemical and functional properties of microvascular endothelial network at the sites of angiogenesis. In comparison with normoxic controls, VVEC from hypoxic animals are characterized by (1) drastically impaired nucleoside triphosphate diphos-phohydrolase-1 (NTPDase-1/CD39) and ecto-5′-nucleotidase/CD73 activities with respective increases in basal extracellular ATP and ADP levels (2) higher proliferative responses to low micromolar concentrations of ATP and ADP; and (3) enhanced permeability and disordered adenosinergic control of vascular barrier function (measured as a paracellular flux of 70 kDa fluorescein isothiocyanate-dextran). Together, these results suggest that unique pattern of purine-mediated angiogenic activation and enhanced leakiness of VVEC from chronically hypoxic vessels may be defined by disordered endothelial nucleotide homeostasis at sites of active neovascularization.
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影响因子：
20.1
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