Background It has been widely demonstrated that endothelial progenitor cells are involved in several diseases and that they have therapeutic implications. In order to define the altered pulmonary vascular homeostasis in chronic obstructive pulmonary disease, we sought to observe the level and functions of circulating endothelial progenitor calls in patients with chronic obstructive pulmonary disease. Methods The total study population included 20 patients with chronic obstructive pulmonary disease and 20 control subjects. The number of circulating endothelial progenitor cells （CD34＋/CD133＋/IVEGFR-2＋cells） was counted by flow cytometry. Circulating endothelial progenitor cells were also cultured in vitro and characterized by uptake of Dil- acLDL, combining with UEA-I, and expression of von Willebrand factor and endothelial nitric oxide synthase. Adhesion, proliferation, production of nitric oxide, and expression of endothelial nitric oxide synthase and phosphorylated-endothelial nitric oxide synthase were detected to determine functions of circulating endothelial progenitor cells in patients with chronic obstructive pulmonary disease. Results The number of circulating endothelial progenitor cells in the chronic obstructive pulmonary disease group was lower than in the control group： （0.54±0.16）% vs. （1.15±0.57）%, P 〈0.05. About 80% of adherent peripheral blood mononuclear cells cultured in vitro were double labeled with Dil-acLDL and UEA-I. The 92% and 91% of them were positive for von Willebrand factor and endothelial nitric oxide synthase, respectively. Compared with the control, there were significantly fewer adhering endothelial progenitor cells in chronic obstructive pulmonary disease patients： 18.7±4.8/field vs. 45.0±5.9/field, P 〈0.05. The proliferation assay showed that the proliferative capacity of circulating endothelial progenitor cells from chronic obstructive pulmonary disease patients was significantly impaired： 0.135±0.038 vs. 0.224±0.042, P 〈0.05. Furthermore, ni
An increasing body of evidence suggests that apoptosis of structural cells in the lung might be an important upstream event in the pathogenesis of chronic obstructive pulmonary disease (COPD).AP-2α is one of the important transcription factors involved in the modulation of apoptosis in carcinogenesis and idiopathic-dilated cardiomyopathy.The relationship between AP-2α and apoptosis in COPD remains to be elucidated.The aim of the present study was to investigate the expression of AP-2α in the lung tissues of rats with COPD induced by smoking and its possible protective effect on cigarette smoke extract (CSE) induced endothelial cell apoptosis.Sprague-Dawley rats (n=24) were randomly assigned to normal and COPD groups.The COPD group was exposed to smoke from 20 commercial unfiltered cigarettes for 80 d before morphological assessment of the lung tissue was performed.The expression of AP-2α in lung tissues was measured by Western blotting.To demonstrate the relationship between apoptosis and AP-2α,in vitro cell experiments were carried out.Cells were treated with different concentrations of CSE before proliferation was measured by MTT.Apoptosis was then determined by Hoechst staining and the expression of cleaved caspase-3 and AP-2α by Western blotting over time following treatment with 5% CSE.Cells were then infected with an AP-2α adenovirus vector and the expression of cleaved caspase-3 and AP-2α was compared to the control groups by Western blotting.The COPD group showed larger air spaces and significant decrease of FEV 0.3/FVC compared with the rats in the control group (P<0.05).The expression of AP-2α was significantly higher in the lung tissue of rats with COPD compared with those of controls (P<0.05).In the ECV304 cells,CSE induced apoptosis (P<0.01) and caspase-3 activation in a time-dependent manner and reduced the cell proliferation rate in a dose-dependent manner (P<0.005).Moreover,5% CSE treatment increased endogenous AP-2α protein expression.AP-2α overexpression inhibited 5% CSE-induced cell
LI JunLi CHEN Yan CHEN Ping CAI Shan PENG Hong ZHOU Rui XIANG XuDong LONG Hong LIU ShaoKun
