Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the possibility that susceptibility to the development of atherosclerosis during chronic renal failure is genetically determined, aortic lesion formation and changes in serum lipid levels in mice of 2 different inbred strains, C57BL/6J and A/J, were examined. Chronic uremia was induced by electrocoagulation of the right renal cortex and left nephrectomy. The mice were then fed either normal rodent chow or a saturated fat and cholesterol-enriched diet for 6 weeks. None of the A/J mice developed atherosclerosis, whereas the aortas of chow-fed uremic C57BL/6J mice were found to contain a number of fatty lesions, the severity of which was increased by a high fat diet. Uremia had different effects on serum cholesterol, triglycerides, and lipoproteins in the two strains. The results suggest that the resistance of A/J mice to uremia-induced atherosclerosis may be attributed to their ability to maintain high serum HDL-cholesterol levels and/or low serum triglyceride levels. The results further indicate that the development of atherosclerotic lesions in uremic mice is both genetically determined and affected by diet.
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PMID:Atherosclerosis in uremic mice. 259 54

Chronic uremia appears to be in a state of an increased oxidative stress. Under oxidative stress, proteins are modified directly by reactive oxygen species with the eventual formation of oxidised amino acids. Proteins are also modified indirectly with reactive carbonyl compounds formed by the autoxidation of carbohydrates and lipids, with the eventual formation of the advanced glycation/lipoxidation end products (AGEs/ALEs). AGEs, pentosidine and carboxymethyllysine (CML), and ALE, malondialdehyde (MDA)-lysine, are elevated in plasma and matrix proteins of uremic patients several times above normal subjects. Precursor carbonyl compounds derived from carbohydrates and lipids are indeed elevated in uremic circulation. Uremia thus appears to be in a state of carbonyl overload with potentially damaging proteins (carbonyl stress). Carbonyl stress might be relevant to long-term complications associated with chronic renal failure and dialysis, such as dialysis-related amyloidosis and atherosclerosis. Immunohistochemical studies identified carbonyl stress in long-lived amyloid deposits and vascular lesions. Proteins modified under carbonyl stress exhibit several biological activities, which might, at least in part, account for the development of joint and vascular complications in uremia.
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PMID:Oxidative protein damage with carbohydrates and lipids in uremia: 'Carbonyl stress'. 1044 66

Oxidative stress is a disturbance of balance between oxidants and antioxidant species. The existence of an increased oxidative stress in chronic renal failure is supported by evidence of increased lipid, carbohydrate, and protein oxidation products in plasma and cell membrane. Recent studies have implicated the oxidative stress in the nonenzymatic biochemistry leading to irreversible protein modifications. Reactive oxygen species may directly alter proteins with the eventual formation of oxidized amino acids. Alternatively, reactive carbonyl compounds formed by the oxidation of carbohydrates and lipids may indirectly lead to advanced glycation or lipoxidation of proteins. Chronic uremia is associated with increased modification of protein caused by reactive carbonyl compounds derived from both carbohydrates and lipids. Increased carbonyl modification of proteins subsequently results in the rise of plasma and tissue contents of advanced glycation end products and advanced lipoxidation end products, in which the deleterious biological effects have been revealed. This article focuses on the irreversible nonenzymatic modification of proteins, which might, at least in part, contribute to the development of complications associated with chronic renal failure and long-term dialysis, such as atherosclerosis and dialysis-related amyloidosis.
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PMID:Relevance of oxidative and carbonyl stress to long-term uremic complications. 1093 8

The causes for the high frequency of cardiovascular disease in dialysis patients are multifactorial in origin. Disturbances in the carbohydrate and lipid metabolism, the balance between oxidants and antioxidants and the immuno-inflammatory system are thought to play a role. Chronic uremia is characterized by the accumulation of advanced glycation end products (AGEs) and advanced oxidation products (AOPP) as well as activation of the acute phase response. High serum levels of these products and acute phase reactants such as C-reactive protein (CRP), fibrinogen and serum amyloid A can be found. CRP has been shown to predict cardiovascular and overall mortality in hemodialysis patients. Whether CRP is involved causally in atherosclerosis or merely represents a marker of disease is as yet unknown. Since CRP has been detected in colocalization with modified apolipoproteins or complement components in atherosclerotic lesions, a pathophysiological role seems very likely. AGEs as well have been detected in aortas of hemodialysis patients. Incubation of endothelial cells with AGEs induced expression of adhesion molecules with consecutive attraction of monocytes to the vessel wall. Thus far, clinical studies investigating the predictive effects of AGEs on cardiovascular mortality in hemodialysis patients are lacking. There is considerable debate about what factors turn on the acute phase response in this population. Proinflammatory effects of AGEs mediated through one receptor for AGEs, RAGE, have been described. We hypothesize that there may be a link between increased hepatic CRP production and the accumulation of AGEs in uremia. AGEs may stimulate CRP production in hepatocytes either directly or indirectly via interaction with monocytes.
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PMID:Inflammation and advanced glycation end products in uremia: simple coexistence, potentiation or causal relationship? 1116 79

There is a growing recognition that uremia is a proinflammatory condition. Chronic uremia-associated inflammation contributes to the pathogenesis of atherosclerosis, anemia, and cardiovascular calcification in patients with end stage renal failure. Many clinical and experimental evidences indicate that the higher the inflammatory status, the higher is morbidity, mortality and the incidence of chronic malnutrition. Aim of this review is to address the main clinical and experimental findings of the effect of chronic inflammation on clinical outcome in dialysis patients.
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PMID:[Effect of inflammation on clinical outcomes in dialysis patients]. 1686 6