Proproliferative phenotype of pulmonary microvascular endothelial cells.

Proproliferative phenotype of pulmonary microvascular endothelial cells.
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肺微血管内皮细胞的增殖表型。

DOI:
10.1152/ajplung.00304.2006
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发表时间:
2007
期刊:
American journal of physiology. Lung cellular and molecular physiology
影响因子:
--
通讯作者:
Fouty,Brian
Fouty,Brian
中科院分区:
--
文献类型:
--
作者:
Solodushko,Victor;Fouty,Brian

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内皮细胞有许多重要的功能,包括释放血管扩张剂、控制凝血级联、限制溶质和液体从血管外空间流出。在肺微循环中,体液平衡的调节尤其重要,在微循环中,内皮屏障功能的丧失可导致肺泡充血和危及生命的低氧血症。然而,微循环内皮细胞和较大肺动脉细胞之间存在显著的异质性,这些差异可能与血管损伤后屏障功能的恢复有关。利用从肺微循环(肺微血管内皮细胞(PMVEC))和较大肺动脉(肺动脉内皮细胞(PAEC))中收集的明确的大鼠内皮细胞群,我们比较了它们在低血清条件下的生长特性。停用血清可抑制PAEC细胞的增殖并诱导G0/ g1阻滞,而PMVEC细胞未发生G0/ g1阻滞,继续增殖。与此观察结果一致,相对于PAEC, PMVEC具有高磷酸化(无活性)视网膜母细胞瘤(Rb)的cdk4和cdk2激酶活性增加,以及周期蛋白D1蛋白水平增加三倍;cdk抑制剂p21Cip1/ waf1和p27kip1的过表达诱导G0/ g1阻滞。在非融合性PMVEC中,血清停药不能诱导G0/ g1停止,而融合性PMVEC与低磷酸化Rb和生长停止相关;失去融合导致恢复增长。这些数据表明,不融合的PMVEC继续独立于生长因子增殖。这种增生性可能对内皮损伤后肺微循环汇合(和屏障功能)的恢复很重要。
Endothelial cells perform a number of important functions including release of vasodilators, control of the coagulation cascade, and restriction of solutes and fluid from the extravascular space. Regulation of fluid balance is of particular importance in the microcirculation of the lung where the loss of endothelial barrier function can lead to alveolar flooding and life-threatening hypoxemia. Significant heterogeneity exists between endothelial cells lining the microcirculation and cells from larger pulmonary arteries, however, and these differences may be relevant in restoring barrier function following vascular injury. Using well-defined populations of rat endothelial cells harvested from the pulmonary microcirculation [pulmonary microvascular endothelial cells (PMVEC)] and from larger pulmonary arteries [pulmonary artery endothelial cells (PAEC)], we compared their growth characteristics in low serum conditions. Withdrawal of serum inhibited proliferation and induced G0/G1arrest in PAEC, whereas PMVEC failed to undergo G0/G1arrest and continued to proliferate. Consistent with this observation, PMVEC had an increased cdk4 and cdk2 kinase activity with hyperphosphorylated (inactive) retinoblastoma (Rb) relative to PAEC as well as a threefold increase in cyclin D1 protein levels; overexpression of the cdk inhibitors p21Cip1/Waf1and p27Kip1induced G0/G1arrest. While serum withdrawal failed to induce G0/G1arrest in nonconfluent PMVEC, confluence was associated with hypophosphorylated Rb and growth arrest; loss of confluence led to resumption of growth. These data suggest that nonconfluent PMVEC continue to proliferate independently of growth factors. This proliferative characteristic may be important in restoring confluence (and barrier function) in the pulmonary microcirculation following endothelial injury.
环 GMP 特异性磷酸二酯酶 5 调节肺内皮细胞的生长和凋亡。
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发表时间: 2002-12-01
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DOI: --
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影响因子: --
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发表时间: 1998-11-15
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