Mechanical, cellular, and molecular factors interact to modulate circulating endothelial cell progenitors.

Mechanical, cellular, and molecular factors interact to modulate circulating endothelial cell progenitors.
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机械、细胞和分子因素相互作用来调节循环内皮细胞祖细胞。

DOI:
10.1152/ajpheart.00431.2003
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发表时间:
2004
期刊:
American journal of physiology. Heart and circulatory physiology
影响因子:
--
通讯作者:
Schatteman,GinaC
Schatteman,GinaC
中科院分区:
--
文献类型:
--
作者:
Wang,Chunlin;Jiao,Chunhua;Hanlon,HeatherD;Zheng,Wei;Tomanek,RobertJ;Schatteman,GinaC

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似乎存在两类人循环内皮细胞(EC)祖细胞,CD 34+和CD 34-CD 14+细胞。注意力集中在CD 34+细胞上,然而CD 34-CD 14+单核细胞要丰富得多,并且可能代表最常见的循环EC祖细胞类别。关于调节假定的CD 34-CD 14 +EC祖细胞功能的分子或生理因素知之甚少,尽管其他血液和心血管细胞分泌的因子可能会影响它们的行为。缺氧和牵张是两种重要的生理刺激,已知可触发心血管细胞中的生长因子,并因此可调节EC祖细胞。为了研究这些环境参数对EC祖细胞的影响,评价了CD 34-CD 14+培养物中的EC产生。我们的数据表明,无论是拉伸或缺氧改变EC祖细胞直接EC生产,但这样做间接通过他们对心血管细胞的影响。来自冠状动脉平滑肌细胞的条件培养基(CM)抑制培养物中EC的产生,并且如果冠状动脉平滑肌细胞已经经受周期性拉伸,则这种抑制更强。相比之下,心肌细胞CM增加EC细胞数量,如果心肌细胞已经经受缺氧,则这种效果会增强。值得注意的是,EC祖细胞对CM的反应因CD 34-CD 14-外周血单核细胞(PBMC)的存在而改变。此外,CD 34-CD 14-PBMCs可减弱EC祖细胞对血管生成因子碱性成纤维细胞生长因子(FGF-2)、血管内皮细胞生长因子-A165和促红细胞生成素的反应性,同时在体外存在转化生长因子-β 1时诱导EC祖细胞死亡
It appears that there are two classes of human circulating endothelial cell (EC) progenitors, CD34+and CD34–CD14+cells. Attention has focused on CD34+cells, yet CD34–CD14+monocytic cells are far more abundant and may represent the most common class of circulating EC progenitor. Little is known about molecular or physiological factors that regulate putative CD34–CD14+EC progenitor function, although factors secreted by other blood and cardiovascular cells to which they are exposed probably affect their behavior. Hypoxia and stretch are two important physiological stimuli known to trigger growth factors in cardiovascular cells and accordingly may modulate EC progenitors. To investigate the impact of these environmental parameters on EC progenitors, EC production in CD34–CD14+cultures was evaluated. Our data indicate that neither stretch nor hypoxia alters EC production by EC progenitors directly but do so indirectly through their effects on cardiovascular cells. Conditioned media (CM) from coronary artery smooth muscle cells inhibit EC production in culture, and this inhibition is stronger if the coronary smooth muscle cells have been subjected to cyclic stretch. In contrast, cardiomyocyte CM increases EC cell number, an effect that is potentiated if the myocytes have been subjected to hypoxia. Significantly, EC progenitor responses to CM are altered by the presence of CD34–CD14–peripheral blood mononuclear cells (PBMCs). Moreover, CD34–CD14–PBMCs attenuate EC progenitor responsiveness to the angiogenic factors basic fibroblast growth factor (FGF-2), vascular endothelial cell growth factor-A165, and erythropoietin while inducing EC progenitor death in the presence of transforming growth factor-β1in vitro
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