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

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 BD 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-alpha, 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-alpha 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-a might have specific inhibitory actions on EPC in both HD patients and healthy controls. No relationship was present between EPC and endothelial dysfunction/atherosclerosis.