| Cardiovascular disease (CVD) is the leading cause of death in patients with end-stage renal disease (ESRD) that require dialysis, at a risk that is 10- to 20-fold the age and sex matched general population. Studies evaluating coronary calcification by electron beam computed tomography (EBCT) in patients with ESRD have demonstrated two- to five- fold more coronary calcification than age-αnd sex- matched individuals with angiographically-proven coronary artery disease. Goodman et al recently demonstrated that this process also affected young adults on dialysis, with a sharp increase in the magnitude of coronary artery calcification by EBCT after age 20. In dialysis patients, the presence of extra-skeletal calcification has been previously attributed to metastatic calcification, whereby the elevated concentrations of calcium and phosphorus in the serum of dialysis patients leads to supersaturation and subsequent deposition in the form of hydroxyapatite. However, recent studies have found the production of bone matrix protein by vascular muscle cell. This imply vascular calcification is not a simply metastic, but rather than an active process.There are many risk factors involved in cardiovascular calcification, such as age, cigarettesmoking, hypertension, diabetes mellitus, and/or glucose intolerance, and disturbances in lipid metabolism. Much clinical observation revealed that hyperphosphatemia is highly correlated with the extent of vascular calcification and vascular disease. The molecular mechanisms regulation vascular calcification is currently the subject of intense investigation.Inflammation is now recognized as an integral component of atherosclerosis and whether it can aggravate cardiovascular calcification is now under intense investigation. Several clinical observations revealed that peritoneal dialysis patients with higher CRP increase the risk of valve calcification and coronary calcification. Inflammation may reduce fetuin-A, which serves to maintain the solubility of calcium in plasma to facilitate vascular and soft tissues calcification. TNF-a , a pleiotropic cytokine was detected in the calcified artherosclerosis plaque. But whether it can promote calcification and what is its mechanism is not very clear.In this paper, in part one, we utilized multi-slice spiral CT to quantify analysis coronary artery calcification of ESRD patients and analyze clinical related factors. In part two, we examined the inferior epigastric artery removed during the transplant procedure and compare histologic findings with clinical parameter, laboratory tests, cytokine and related protein and try to find the association between medial artery calcification in ESRD patients and deposition of bone matrix proteins and chronic inflammation. In part three, rat vascular smooth muscles cell were treated with different Pi levels and with/without TNF-a to test its effect on calcification and further clarify its molecular regulation mechanisms.Part 1 Quantification analysis of coronary artery calcification in uraemic patientsMaterials and methods1. ObjectsNinety-four patients with end stage renal disease (ESRD) from Dec. 2001 to Nov. 2002 were eligible for the study. Forty-two patients were on maintenance hemodialysis (MHD) treatment and fifty-two were pre-hemodialysis ESRD patients (PHD).2. Methods2.1 Detection of coronary artery calcification (CAC) : CAC Scores were evaluated by multi-slice spiral CT (MSCT) and calculated according to Agatston method. Calcification of mitral valve was evaluated too.2.2 CAC grading: CAC grading was based on Rumberger s method,, less than 1 : no calcification; 1 to 100: mild calcification; more than 100: moderate to severe calcification.2.3 Serum calcium, phosphorus (Pi), triglyceride (TG), total cholesterol and low-density lipoprotein (LDL) were analyzed by colorimetric methods using auto-analyzer. IPTH was analyzed by radio-immune assay.3 The relationship between CAC and cardio-vascular complication: The incidence o...
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