慢性血液透析患者中，内皮祖细胞减少与炎症相关，但与内皮功能障碍无关。

Decrease in endothelial progenitor cells associated with inflammation, but not with endothelial dysfunction in chronic hemodialysis patients.

作者信息

Ozkok Abdullah, Aktas Esin, Yilmaz Akar, Telci Aysegul, Oflaz Huseyin, Deniz Gunnur, Yildiz Alaattin

机构信息

Department of Internal Medicine, Istanbul School of Medicine, Istanbul University, Istanbul, Turkey.

出版信息

Clin Nephrol. 2013 Jan;79(1):21-30. doi: 10.5414/CN107318.

DOI:10.5414/CN107318

PMID:22909781

Abstract

INTRODUCTION

Endothelial progenitor cells (EPC), bone marrow derived cells, are considered to have a pivotal role in maintaining the integrity and repair of the endothelium. Endothelial dysfunction, atherosclerosis and inflammation are implicated for increased CV mortality in uremia. In this study, we aimed to investigate the possible association of EPC with inflammation, endothelial dysfunction and atherosclerosis in chronic hemodialysis (HD) patients.

PATIENTS AND METHODS

67 HD patients (male/female: 30/37, mean age: 58 ± 15 years) and 22 healthy controls (male/female: 13/9; mean age: 48 ± 8 years) were included. EPC were cultivated in the fibronectin-covered culture dishes and counted. Also EPC markers were studied by flow cytometry using anti-CD34, anti-CD133 and anti-vascular endothelial growth factor receptor 2 (VEGFR-2) antibodies. Serum levels of IL-6, TNF-α, intercellular cell adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM) and asymmetric dimethyl-arginine (ADMA) were measured by ELISA method. Endothelial function was investigated by measuring flow-mediated dilatation (FMD) of the brachial artery. Carotid intima-media thickness (CIMT) and ratio (CIMR) were also examined.

RESULTS

EPC number was decreased in HD patients when compared to controls (63.7 ± 8.9 vs. 101.5 ± 19.6/ high power field, p < 0.001). Also CD34+ cell count was significantly lower in the HD group (2.26 ± 3.52 vs. 6.03 ± 4.73%, p < 0.0001). EPC number was significantly inversely correlated with serum TNF-α levels in HD patients(r: -0.453, p < 0.001) and also in the control group (r = -0.509, p = 0.044). There was an inverse association between VEGFR-2+/CD34+cell count and serum IL-6 levels (r: -0.364, p = 0.006) in HD patients. However, EPC count was not related to FMD and CIMT/CIMR. In HD patients, there was a positive correlation between serum IL-6 levels with CIMT (r = 0.358, p = 0.01) and CIMR was positively correlated with serum ICAM (r = 0.430, p = 0.002).

CONCLUSION

EPC number was decreased in uremia and was associated with inflammation. TNF-α might have specific inhibitory actions on EPC in both HD patients and healthy controls. No relationship was present between EPC and endothelial dysfunction/atherosclerosis.

摘要

引言

内皮祖细胞（EPC）是源自骨髓的细胞，被认为在维持内皮的完整性和修复中起关键作用。内皮功能障碍、动脉粥样硬化和炎症与尿毒症患者心血管死亡率增加有关。在本研究中，我们旨在调查慢性血液透析（HD）患者中EPC与炎症、内皮功能障碍和动脉粥样硬化之间可能存在的关联。

患者与方法

纳入67例HD患者（男/女：30/37，平均年龄：58±15岁）和22例健康对照者（男/女：13/9；平均年龄：48±8岁）。将EPC接种于纤连蛋白包被的培养皿中并计数。同时，使用抗CD34、抗CD133和抗血管内皮生长因子受体2（VEGFR-2）抗体通过流式细胞术研究EPC标志物。采用ELISA法测定血清白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、细胞间黏附分子（ICAM）、血管细胞黏附分子（VCAM）和不对称二甲基精氨酸（ADMA）水平。通过测量肱动脉的血流介导的扩张（FMD）来研究内皮功能。还检查了颈动脉内膜中层厚度（CIMT）和比值（CIMR）。

结果

与对照组相比，HD患者的EPC数量减少（63.7±8.9对101.5±19.6/高倍视野，p<0.001）。HD组中CD34+细胞计数也显著降低（2.26±3.52对6.03±4.73%，p<0.0001）。HD患者中EPC数量与血清TNF-α水平呈显著负相关（r：-0.453，p<0.001），在对照组中也是如此（r=-0.509，p=0.044）。HD患者中VEGFR-2+/CD34+细胞计数与血清IL-6水平呈负相关（r：-0.364，p=0.006）。然而，EPC计数与FMD和CIMT/CIMR无关。在HD患者中，血清IL-6水平与CIMT呈正相关（r=0.358，p=0.01），CIMR与血清ICAM呈正相关（r=0.430，p=0.002）。