Correlation between endothelin-1 and atherosclerosis in chronic hemodialysis patients

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.