| BackgroundCardiovascular diseases are the most common complications seen in patients with end-stage renal disease (ESRD), whose death rate were 16.6-17.7 fold as high as the general population. According to the statistics by US Renal Data system (USRDS) in 1999, cardiovascular diseases accounted for 45% the cause of ESRD patient deaths. The primary etiological factor and age distribution of ESRD in China are much different from those in western countries, however, the death rate due to cardiovascular diseases was about 50% in ESRD patients, according to the CSN's (Chinese Association of Nephrology) register of dialysis and transplantation in the identical year. Therefore, cardiovascular diseases have become the most important factor affecting the survival rate and mutilation rate for ESRD patients.The incidence rate of cardiovascular diseases is 5-10 times higher in ESRD patients than that in the general population. Because of the high morbidity and early onset, it is also called "accelerated atherosclerosis". Although the causes of the cardiovascular diseases are incompletely known, clinical epidemiological studies in recent 10 years provided us a in-depth understanding of the risk factors in ESRD. Many of the causes of vasculopathy in ESRD patients are the same as those in the genera population, such as hypertension, diabetes mellitus, and hyperlipidemia, but some appear to have special relation to chronic uremia including the hemodynamicdisorders caused by anemia and hypervolemia, hyperhomocystinemia,10oxidative stress and inflammatory state. Therefore, ESRD is thought as a vasculopathic state.Data of our and other laboratories have shown the circular levels of advanced glycation end products (AGEs) in ESRD patients are abnormally elevated and AGE precipitations were found in the vessel walls of ESRD patients suffered with atherosclerosis. AGEs are the end products of nonenzymatical glycation and oxidation reacted between the amino groups of proteins and the aldehyde groups of sugars. The initial Schiff base undergoes rearrangement to form relatively stable ketoamines, the Amadori products. These glycated proteins undergo progressive dehydration, cyclization, oxidation and rearrangement to form AGEs. AGE modified proteins show the properties of promoting expressions of adhesive molecules and E-selectin, increasing vascular permeability, inactivating the activity of endothelial nitric oxide synthase and damaging its mRNA stability in vitro. These evidences imply that AGE is a kind of uremic toxins that may have important pathophysiological effect to endothelial cells.The mechanisms of the accelerated atherosclerosis (AS) are incompletely understood. Recent studies have shown the AS is an inflammatory disease. The early AS has two stages: (1) The endothelial dysfunction results from various injuries. Nitric oxide (NO) released by the endothelial cells is indispensable for the endothelia cells maintaining the normal vascular homeostatic state. NO is the active moiety of the endothelial-derived relaxing factor involved in regulation of vascular tone, inhibition of platelet aggregation and monocyte adhesiveness, which makes it the most important anti-atherosclerosis factor. The changes in production will inevitably affectthe normal preventive properties of blood vessels, inducing the abnormalities11in vascular structure and function. The AS patients usually have damages in NO production, which results in an elevated adhesiveness of endothelial cells with platelets and inflammatory cells. (2) In the second stage, endothelial cells express monocyte chemoattractant protein-1 and adhesive molecules, inducing monocytes aggregation and migration. The monocytes transform to macrophages and also secret MCP-1, increasing the local MCP-1 concentration and attracting more monocytes. Thus the inflammation is enlarged. Considering of the important role of NO and MCP-1 on the pathogenesis of AS, we hypothesize that elevated AGE modified protein levels seen in ESRD patients contribute to the acce...
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