慢性阻塞性肺疾病患者循环内皮祖细胞减少和功能障碍。
Decreased and dysfunctional circulating endothelial progenitor cells in patients with chronic obstructive pulmonary disease.
机构信息
Department of Geriatrics, Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.
出版信息
Chin Med J (Engl). 2013;126(17):3222-7.
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 cells 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(+)/VEGFR-2(+) cells) was counted by flow cytometry. Circulating endothelial progenitor cells were also cultured in vitro and characterized by uptake of DiIacLDL, 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-1. 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, nitric oxide synthase (112.06 ± 10.00 vs. 135.41 ± 5.38, P < 0.05), phosphorylated endothelial nitric oxide synthase protein expression (88.89 ± 4.98 vs. 117.98 ± 16.49, P < 0.05) and nitric oxide production ((25.11 ± 5.27) µmol/L vs. (37.72 ± 7.10) µmol/L, P < 0.05) were remarkably lower in endothelial cells from the chronic obstructive pulmonary disease group than the control.
CONCLUSION
Circulating endothelial progenitor cells were decreased and functionally impaired in patients with chronic obstructive pulmonary disease.
背景
已有研究表明内皮祖细胞参与多种疾病的发生发展，具有潜在的治疗意义。为了明确慢性阻塞性肺疾病中肺血管稳态的改变，我们观察了慢性阻塞性肺疾病患者外周血循环内皮祖细胞的水平及其功能。
方法
总研究人群包括 20 例慢性阻塞性肺疾病患者和 20 例对照。通过流式细胞术计数循环内皮祖细胞（CD34+ / CD133+ / VEGFR-2+ 细胞）的数量。还将循环内皮祖细胞在体外培养，并通过摄取 DiIacLDL、结合 UEA-I 以及表达血管性血友病因子和内皮型一氧化氮合酶来进行鉴定。检测黏附、增殖、一氧化氮生成以及内皮型一氧化氮合酶和磷酸化内皮型一氧化氮合酶的表达，以确定慢性阻塞性肺疾病患者循环内皮祖细胞的功能。
结果
与对照组相比，慢性阻塞性肺疾病组的循环内皮祖细胞数量较低：（0.54 ± 0.16）% vs. （1.15 ± 0.57）%，P < 0.05。体外培养的约 80%贴壁外周血单个核细胞双标 Dil-acLDL 和 UEA-1。其中 92%和 91%分别为血管性血友病因子和内皮型一氧化氮合酶阳性。与对照组相比，慢性阻塞性肺疾病患者的黏附内皮祖细胞明显减少：18.7 ± 4.8/视野 vs. 45.0 ± 5.9/视野，P < 0.05。增殖试验表明，慢性阻塞性肺疾病患者循环内皮祖细胞的增殖能力明显受损：0.135 ± 0.038 vs. 0.224 ± 0.042，P < 0.05。此外，一氧化氮合酶（112.06 ± 10.00 vs. 135.41 ± 5.38，P < 0.05）、磷酸化内皮型一氧化氮合酶蛋白表达（88.89 ± 4.98 vs. 117.98 ± 16.49，P < 0.05）和一氧化氮生成（（25.11 ± 5.27）µmol/L vs. （37.72 ± 7.10）µmol/L，P < 0.05）在慢性阻塞性肺疾病组的内皮细胞中明显低于对照组。
结论
慢性阻塞性肺疾病患者的循环内皮祖细胞数量减少且功能受损。
Zotero 插件