CD133+cells are associated with ADIPOCYTOKINES and endothelial dysfunction in hemodialysis patients

Abstract

Background: Hemodialysis (HD) patients have increased risk of cardiovascular disease (CVD). Impaired stem cell health and adipocytokine metabolism may play important roles in the complex pathophysiological mechanisms of CVD in this patient population. We aimed to investigate the relationships between CD133+ cell counts, adipocytokines and parameters of endothelial dysfunction and atherosclerosis in HD patients. Methods: In 58 chronic HD patients (male/female: 28/30, mean age: 58 +/- 14 years), serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), leptin, adiponectin and resistin were measured by ELISA. Left ventricular mass index (LVMI), carotid intima-media thickness (CIMT), flow-mediated dilatation (FMD) of the brachial artery were measured. CD133+ cells were counted by flow cytometry (BD FACSCalibur-BD Bioscience, CA). Results: CD133+ cell counts were inversely associated with FMD (r = -0.39, p = 0.007) and positively correlated with serum resistin (r = 0.45, p < 0.001) and serum TNF-alpha (r = 0.31, p = 0.02). Serum leptin levels were higher in high CD133 group compared to low CD133 group [32.37(12.74-72.29) vs 15.50(5.38-37.12) ng/mL, p = 0.03]. Serum leptin levels were correlated with TNF-alpha(r = 0.35, p = 0.009). Serum adiponectin levels were negatively correlated with serum leptin (r = -0.28, p = 0.03). Serum resistin levels were associated with TNF-alpha (r = 0.54, p < 0.001) and leptin (r = 0.29, p = 0.03). Serum IL-6 levels were significantly associated with LVMI (r = 0.31, p = 0.03). Serum IL-6 levels were significantly higher in patients with carotid plaque compared to patients without plaque [12.75(9.91-28.68) vs 8.27(5.97-14.04) pg/mL, p = 0.02]. In multiple linear regression analysis to determine the factors predicting LogFMD; dialysis vintage, LVMI and LogCD133+ cell counts were included as independent variables(R = 0.57, adjusted R-square = 0.27, p = 0.001). CD133+ cell count and LVMI were found to significantly predict FMD (p = 0.03 and p = 0.04 respectively). Conclusion: CD133+ cells were associated with inflammation and endothelial dysfunction in HD patients. Serum leptin, resistin and TNF-alpha levels were positively related to CD133+ cell count. Impaired regulation of undifferentiated stem cells and adipocytokines might contribute to endothelial dysfunction in HD patients.