Davie Neil J, Crossno Joseph T, Frid Maria G, Hofmeister Stephen E, Reeves John T, Hyde Dallas M, Carpenter Todd C, Brunetti Jacqueline A, McNiece Ian K, Stenmark Kurt R
Developmental Lung Biology Group, UCHSC, 4200 East 9(th) Ave., Rm. 3419, Denver, CO 80262, USA.
Am J Physiol Lung Cell Mol Physiol. 2004 Apr;286(4):L668-78. doi: 10.1152/ajplung.00108.2003. Epub 2003 May 16.
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.
关于动脉滋养血管在多种全身性血管疾病中的重要作用，相关信息正在迅速涌现。此外，越来越多的证据表明，骨髓来源的祖细胞可能参与了某些形式的全身性血管疾病所特有的出生后新血管形成和/或血管壁增厚过程。关于出生后滋养血管形成以及骨髓来源的祖细胞在肺动脉高压（PH）情况下的作用，目前所知甚少。我们试图确定慢性缺氧对肺动脉中滋养血管密度的影响，并评估在缺氧诱导的PH牛模型中，骨髓来源的祖细胞是否促成了血管壁质量的增加。对常氧和缺氧小牛的肺组织进行定量形态学分析发现，缺氧导致肺动脉外膜滋养血管显著扩张。流式细胞术分析表明，表达干细胞因子跨膜酪氨酸激酶受体c-kit的细胞在缺氧刺激下从骨髓动员至循环中。免疫组织化学显示，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。从暴露于缺氧环境的新生小牛中分离出的循环单核细胞，根据培养条件可分化为内皮细胞和平滑肌细胞表型。基于这些观察结果，我们认为滋养血管和循环祖细胞可能参与了缺氧诱导的PH情况下的血管壁增厚过程。
