Significance of the Level of Monocyte Chemoattractant Protein-1 in Human Atherosclerosis-Assessment in Chronic Hemodialysis Patients-

Abstract

he rates of cardiovascular or cerebrovascular mortality related to accelerated atherosclerosis are high in patients undergoing chronic hemodialysis (HD) treatment. 1,2 The overall cardiovascular mortality rate in patients undergoing chronic HD treatment is estimated to be approximately 30%, of which 10% are deaths because of myocardial infarction. 3 Recently, it has been shown that monocyte chemoattractant protein-1 (MCP-1) is a potent monocyte chemoattractant and largely responsible for the recruitment of monocytes/macrophages to the vessel wall in the early stage of atherogenesis. [4][5][6][7][8][9][10][11][12] In the clinical setting, it has been reported that the plasma concentrations of several cytokines and chemokines, including MCP-1, increased during long-term HD treatment. 13 However, there have been few studies of the relationship between the severity of human atherosclerosis and the serum concentration of MCP-1 in HD patients. 13,14 High-resolution ultrasound imaging is now a reliable means of directly examining and quantifying pre-clinical Circulation Journal Vol. 68, July 2004 atherosclerotic lesions in peripheral arteries. 15 This method is noninvasive and has high reproducibility. 16 Ultrasound measurements of intimal -medial thickness (IMT) in the carotid artery have been used as indicators of coronary atherosclerosis. 17 Tabara et al reported that the plasma concentration of MCP-1 was significantly associated with IMT in community-based subjects, aged 50 years or older and free from any cardiovascular complications. 18 In the present study, we measured IMT and investigated the effects of MCP-1 and other factors on the severity of IMT in HD patients. We also used immunohistochemistry to investigate the expression of MCP-1 in arterial tissue samples. Methods SubjectsAfter obtaining informed consent, 52 Japanese uremic patients undergoing chronic HD (29 men and 23 women; mean age, 56±10 years: HD group) and 20 age-matched control subjects (9 men and 11 women; mean age, 57±13 years: control group) were enrolled. In the patients undergoing chronic HD, the diagnosed kidney diseases were chronic glomerulonephritis in 47 patients and polycystic kidney disease in 5 patients. To avoid the influence of the cause of the disease, patients with diabetic nephropathy and hypertensive nephrosclerosis were excluded. Patients had been treated by HD 3 times a week for a mean duration of 10.1±7.4 years. The clinical and biochemical characteristics of the patients are summarized in Background Monocyte chemoattractant protein-1 (MCP-1), a potent chemoattractant for monocytes, plays an important role in the earliest events of atherogenesis. However, direct evidence of the effects of MCP-1 on atherosclerosis in chronic hemodialysis (HD) patients has not been reported. Methods and ResultsThe serum MCP-1 concentrations and the intimal -medial thickness (IMT) in the carotid arteries were measured in 42 non-diabetic chronic HD patients and 20 age-matched controls. The expression of MCP-1 was examined immunohistochemicall...

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