Fadini Gian Paolo, Schiavon Marco, Cantini Marcella, Baesso Ilenia, Facco Monica, Miorin Marta, Tassinato Mauro, de Kreutzenberg Saula Vigili, Avogaro Angelo, Agostini Carlo
Department of Clinical and Experimental Medicine, Division of Metabolic Diseases, University of Padova School of Medicine, Italy.
Stem Cells. 2006 Jul;24(7):1806-13. doi: 10.1634/stemcells.2005-0440. Epub 2006 Apr 6.
Patients with chronic severe lung disease are prone to develop pulmonary vascular remodeling, possibly through pulmonary endothelial dysfunction. Circulating endothelial progenitor cells (EPCs) are involved in maintenance of endothelial homeostasis. The aim of this study was to assess whether obstructive and restrictive lung diseases are associated with modification of EPC number in peripheral blood. The study was cross-sectional and involved patients with obstructive (n = 15) and restrictive (n = 15) lung disease on oxygen therapy and 15 control subjects. Circulating EPCs were defined by the surface expression of CD34, CD133, and kinase-insert domain receptor. Results from spirometric tests, blood gas analyses, and blood cell counts have been related to EPC numbers. Patients with chronic hypoxia and severe lung disease showed lower levels of all progenitors than do control subjects. A consensual further reduction of EPC was found in restrictive patients in comparison with obstructive patients. Among restrictive patients, EPC reduction was related to reduced lung volumes and impaired alveolo-arterial diffusion, whereas progenitor cell levels were directly related to erythrocyte number. Considering obstructive patients, significant correlations were found between progenitor cell levels and bronchial obstruction and between progenitor cell levels and arterial oxygen tension. These findings demonstrate a reduction of EPCs in patients with chronic lung disease and long-lasting hypoxia. This alteration was more evident in restrictive patients and correlated to disease severity. Depletion of circulating EPCs may be involved in altered endothelial homeostasis of pulmonary circulation in these disorders.
慢性重症肺病患者易于发生肺血管重塑，可能是通过肺内皮功能障碍实现的。循环内皮祖细胞（EPCs）参与内皮稳态的维持。本研究的目的是评估阻塞性和限制性肺病是否与外周血中EPC数量的改变有关。该研究为横断面研究，纳入了接受氧疗的阻塞性肺病患者（n = 15）、限制性肺病患者（n = 15）以及15名对照受试者。循环EPCs通过CD34、CD133和激酶插入结构域受体的表面表达来定义。肺量计测试、血气分析和血细胞计数的结果与EPC数量相关。慢性缺氧和重症肺病患者的所有祖细胞水平均低于对照受试者。与阻塞性患者相比，在限制性患者中发现EPC进一步一致减少。在限制性患者中，EPC减少与肺容积减小和肺泡-动脉弥散受损有关，而祖细胞水平与红细胞数量直接相关。对于阻塞性患者，祖细胞水平与支气管阻塞以及祖细胞水平与动脉血氧张力之间存在显著相关性。这些发现表明慢性肺病和长期缺氧患者的EPC减少。这种改变在限制性患者中更为明显，且与疾病严重程度相关。循环EPCs的耗竭可能参与了这些疾病中肺循环内皮稳态的改变。
