Hypoxia-induced pulmonary artery adventitial remodeling and neovascularization: contribution of progenitor cells
Hypoxia-induced pulmonary artery adventitial remodeling and neovascularization: contribution of progenitor cells
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DOI：
10.1152/ajplung.00108.2003
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发表时间：
2004-04-01
影响因子：
4.9
通讯作者：
Stenmark, KR
中科院分区：
文献类型：
--
作者：
Davie, NJ;Crossno, JT;Stenmark, KR
关于动脉血管在各种系统性血管疾病中的重要作用的信息正在迅速出现。此外，越来越多的证据表明，骨髓（BM）来源的祖细胞可能有助于出生后新生血管和/或血管壁增厚，这是某些形式的全身性血管疾病的特征。关于出生后血管的形成和骨髓来源的祖细胞在肺动脉高压（PH）中的作用知之甚少。我们试图确定慢性缺氧对肺动脉血管密度的影响，并评估BM衍生的祖细胞是否有助于在缺氧诱导的PH的牛模型中增加血管壁质量。从常氧和缺氧小牛的肺组织的定量形态学分析显示，缺氧导致肺动脉外膜血管的急剧扩张。流式细胞术分析表明，表达跨膜酪氨酸激酶受体的干细胞因子，c-kit的细胞，动员从骨髓中的循环，以响应缺氧。免疫组化显示，在缺氧诱导的重塑肺动脉血管壁中，c-kit（+）细胞以及血管内皮生长因子、纤连蛋白和凝血酶的表达增加。发现从暴露于缺氧的新生小牛中分离的循环单核细胞根据培养条件分化成内皮细胞和平滑肌细胞表型。从这些观察，我们认为，血管和循环祖细胞可能参与血管壁增厚的设置缺氧诱导的PH。
Information is rapidly emerging regarding the important role of the arterial vasa vasorum in a variety of systemic vascular diseases. In addition, increasing evidence suggests that progenitor cells of bone marrow ( BM) origin may contribute to postnatal neovascularization and/or vascular wall thickening that is characteristic in some forms of systemic vascular disease. Little is known regarding postnatal vasa formation and the role of BM-derived progenitor cells in the setting of pulmonary hypertension (PH). We sought to determine the effects of chronic hypoxia on the density of vasa vasorum in the pulmonary artery and to evaluate if BM-derived progenitor cells contribute to the increased vessel wall mass in a bovine model of hypoxia-induced PH. Quantitative morphometric analyses of lung tissue from normoxic and hypoxic calves revealed that hypoxia results in a dramatic expansion of the pulmonary artery adventitial vasa vasorum. Flow cytometric analysis demonstrated that cells expressing the transmembrane tyrosine kinase receptor for stem cell factor, c-kit, are mobilized from the BM in the circulation in response to hypoxia. Immunohistochemistry revealed an increase in the expression of c-kit(+) cells together with vascular endothelial growth factor, fibronectin, and thrombin in the hypoxia-induced remodeled pulmonary artery vessel wall. Circulating mononuclear cells isolated from neonatal calves exposed to hypoxia were found to differentiate into endothelial and smooth muscle cell phenotypes depending on culture conditions. From these observations, we suggest that the vasa vasorum and circulating progenitor cells could be involved in vessel wall thickening in the setting of hypoxia-induced PH.