Ozkok Abdullah, Atas Riza, Cinar Suzan Adin, Yilmaz Akar, Aktas Esin, Deniz Gunnur, Yildiz Alaattin
Department of Nephrology, Istanbul Medeniyet University, Goztepe Training and Research Hospital, Istanbul, Turkey.
Division of Medicine, Department of Cardiology, Kliniken Calw, Calw, Germany.
BMC Nephrol. 2017 Jul 26;18(1):250. doi: 10.1186/s12882-017-0663-x.
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.
In 58 chronic HD patients (male/female:28/30, mean age:58 ± 14 years), serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), 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).
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-α (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-α(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-α (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).
CD133+ cells were associated with inflammation and endothelial dysfunction in HD patients. Serum leptin, resistin and TNF-α levels were positively related to CD133+ cell count. Impaired regulation of undifferentiated stem cells and adipocytokines might contribute to endothelial dysfunction in HD patients.
血液透析(HD)患者患心血管疾病(CVD)的风险增加。干细胞健康受损和脂肪细胞因子代谢可能在该患者群体CVD复杂的病理生理机制中起重要作用。我们旨在研究HD患者中CD133 +细胞计数、脂肪细胞因子与内皮功能障碍和动脉粥样硬化参数之间的关系。
在58例慢性HD患者(男/女:28/30,平均年龄:58±14岁)中,采用酶联免疫吸附测定法(ELISA)检测血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、瘦素、脂联素和抵抗素水平。测量左心室质量指数(LVMI)、颈动脉内膜中层厚度(CIMT)、肱动脉血流介导的舒张功能(FMD)。采用流式细胞术(BD FACSCalibur - BD Bioscience,加利福尼亚州)计数CD133 +细胞。
CD133 +细胞计数与FMD呈负相关(r = -0.39,p = 0.007),与血清抵抗素(r = 0.45,p <0.001)和血清TNF-α(r = 0.31,p = 0.02)呈正相关。高CD133组血清瘦素水平高于低CD133组[32.37(12.74 - 72.29)对15.50(5.38 - 37.12)ng/mL,p = 0.03]。血清瘦素水平与TNF-α相关(r = 0.35,p = 0.009)。血清脂联素水平与血清瘦素呈负相关(r = -0.28,p = 0.03)。血清抵抗素水平与TNF-α(r = 0.54,p <0.001)和瘦素(r = 0.29,p = 0.03)相关。血清IL-6水平与LVMI显著相关(r = 0.31,p = 0.03)。有颈动脉斑块的患者血清IL-6水平显著高于无斑块患者[12.75(9.91 - 28.68)对8.27(5.97 - 14.04)pg/mL,p = 0.02]。在确定预测LogFMD的因素的多元线性回归分析中;透析龄、LVMI和LogCD133 +细胞计数作为自变量纳入(R = 0.57,调整后R平方 = 0.27,p = 0.001)。发现CD133 +细胞计数和LVMI可显著预测FMD(分别为p = 0.03和p = 0.04)。
CD133 +细胞与HD患者的炎症和内皮功能障碍有关。血清瘦素、抵抗素和TNF-α水平与CD133 +细胞计数呈正相关。未分化干细胞和脂肪细胞因子的调节受损可能导致HD患者的内皮功能障碍。