Division of Nephrology, Second Xiangya Hospital, Central South University, Nephrology Institute of Central South University, Changsha, PRC.
J Nephrol. 2010 Sep-Oct;23(5):593-602.
Recent observations suggest that the atherosclerotic process may involve overexpression of ET-1, which could contribute to the formation of atherosclerosis. The aim of the present report was to examine the possible association between carotid IMT and serum ET-1 level and ET-1 expression in the internal iliac artery (IIA) wall in chronic hemodialysis (HD) patients.
Sixty-eight nondiabetic HD patients and 50 age- and sex-matched healthy normotensive controls participated in the study. Atherosclerotic disease in both groups was assessed by measuring intima-media thickness (IMT) and plaque score of the common carotid arteries using an ultrasound scanner. Levels of serum ET-1, C-reactive protein (CRP), interleukin-6 and lipids profile were measured. Internal iliac artery samples were obtained at the time of renal transplantation. Quantitative expression of ET-1 in internal iliac artery walls was assessed by positive unit (pu) value using an immunohistochemical method. In addition, the IMT and carotid plaque score were analyzed in relation to circulating levels of ET-1 and expression of ET-1 in internal iliac artery walls.
Compared with control subjects, HD patients had significantly increased common carotid artery (CCA)-IMT (p=0.002). Atherosclerotic plaques were detected in 42 (61.76%) of HD patients and in 2 (4%) of controls. In HD patients, a close correlation was found between serum ET-1 level and CRP, IL-6 (p<0.01 and p<0.05, respectively). Also we found a close correlation between ET-1 pu value and CRP, IL-6 (p<0.01 and p<0.05 respectively). In HD patients, CCA-IMT and plaque score were correlated significantly with circulating levels of ET-1 (p<0.001 and p<0.05, respectively) and expression of ET-1 in internal iliac artery walls (p<0.01 and p<0.05, respectively). Multivariate analysis showed that serum ET-1 concentrations and expression of ET-1 in internal iliac artery walls were strong independent correlates of CCA-IMT (p=0.004 and p=0.005, respectively).
In HD patients, the circulating levels of ET-1 and expression of ET-1 in internal iliac artery walls were statistically associated with CRP and IL- 6. Moreover, the circulating levels of ET-1 and expression of ET-1 in internal iliac artery walls were independent predictors of carotid atherosclerosis. The correlations may suggest that increased circulating ET-1 level and upregulated expression of ET-1 in the vasculature could contribute to the formation of atherosclerosis in HD patients.
最近的观察表明，动脉粥样硬化过程中可能存在 ET-1 的过度表达，这可能有助于动脉粥样硬化的形成。本报告的目的是研究慢性血液透析（HD）患者颈总动脉内中膜厚度（IMT）和血清 ET-1 水平与内髂动脉（IIA）壁 ET-1 表达之间的可能相关性。
68 名非糖尿病 HD 患者和 50 名年龄和性别匹配的健康血压正常对照组参加了这项研究。使用超声扫描仪评估两组的动脉粥样硬化疾病，测量颈总动脉内膜中层厚度（IMT）和斑块评分。测量血清 ET-1、C 反应蛋白（CRP）、白细胞介素-6 和血脂谱水平。在肾移植时获得内髂动脉样本。使用免疫组织化学方法通过阳性单位（pu）值评估内髂动脉壁中 ET-1 的定量表达。此外，还分析了循环 ET-1 水平与内髂动脉壁 ET-1 表达之间的关系与颈总动脉 IMT 和颈动脉斑块评分的关系。
与对照组相比，HD 患者的颈总动脉（CCA）-IMT 明显增加（p=0.002）。42 例（61.76%）HD 患者和 2 例（4%）对照组检测到动脉粥样硬化斑块。在 HD 患者中，血清 ET-1 水平与 CRP、IL-6 之间存在密切相关性（p<0.01 和 p<0.05）。此外，我们还发现 ET-1 pu 值与 CRP、IL-6 之间存在密切相关性（p<0.01 和 p<0.05）。在 HD 患者中，CCA-IMT 和斑块评分与循环 ET-1 水平（p<0.001 和 p<0.05）和内髂动脉壁 ET-1 表达（p<0.01 和 p<0.05）呈显著相关。多元分析显示，血清 ET-1 浓度和内髂动脉壁 ET-1 表达是 CCA-IMT 的强独立相关因素（p=0.004 和 p=0.005）。
在 HD 患者中，循环 ET-1 水平和内髂动脉壁 ET-1 表达与 CRP 和 IL-6 呈统计学相关。此外，循环 ET-1 水平和内髂动脉壁 ET-1 表达是颈动脉粥样硬化的独立预测因子。这些相关性表明，循环 ET-1 水平升高和血管中 ET-1 表达上调可能有助于 HD 患者动脉粥样硬化的形成。
