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)

Uraemic patients suffer from haemorrhagic disorders and accelerated atherosclerosis. To evaluate the possible role of the vessel wall in these haemostatic alterations associated with uraemia, we investigated the effect of a uraemic milieu on human endothelial cell (EC) cultures and the reactivity of the extracellular matrices (ECM) generated by these cells towards platelets. EC cultures were exposed to a pool of sera (20% in the culture medium) obtained either from uraemic patients or from normal donors, and the following parameters were evaluated: (1) EC viability (trypan blue exclusion test); (2) von Willebrand factor (vWF) levels in supernatants and associated with ECM; (3) the reactivity of EC and EC-derived ECM towards platelets, measured 'ex vivo' under flow conditions (5 min, wall shear rate 800 s-1); and (4) ultrastructure of the ECM. The viability of EC cultured in the presence of uraemic sera was similar to controls. Platelet interaction with ECM generated by EC exposed to uraemic sera was significantly reduced (P < 0.05). This decrease was mainly related to a reduction in platelet adhesion (9.8 +/- 1.9% vs 16.7 +/- 1.8% in controls, P < 0.02). VWF levels in supernatants and associated with ECM were similar to controls. Ultrastructural analysis of the ECM generated by EC exposed to uraemic sera revealed a deficient matrix. An increased removal of EC was observed in experiments in which EC cultured in the presence of uraemic sera were perfused with citrated blood. These results indicate that a uraemic milieu induces quantitative and qualitative changes in the vascular subendothelium, characterized by a less intrincate network of fibrils, as well as a decreased attachment of EC and reduced thrombogenicity to the ECM. These changes may represent another mechanism which contributes to the haemostatic dysfunction observed in uraemic patients.
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PMID:Uraemic medium causes endothelial cell dysfunction characterized by an alteration of the properties of its subendothelial matrix. 880 11

In patients with end-stage renal failure (ESRF), the incidence of atherosclerosis and cancer is increased. The importance of lipid peroxidation (LPO) products in the pathogenesis of these complications has recently been emphasized. The LPO products malondialdehyde (MDA) and hexanal, lipophilic antioxidants and erythrocyte glutathione (GSH) were estimated in 10 pediatric hemodialysis (HD) patients before and after HD and in 11 peritoneal dialysis (CPD) patients. Before HD, MDA was elevated [median (interquartile range): 384.5 (110 to 501) nM; normal < 150 nM], whereas plasma hexanal levels were normal in all patients [130.5 (88 to 222) nM; < 320 nM]. HD decreased MDA concentrations on average by 88% but did not change hexanal levels. CPD patients exhibited high plasma MDA concentrations [371 (287 to 468) nM], whereas hexanal was in the low normal range [56 (51 to 81) nM]. Antioxidants were normal in both groups and unchanged during HD. GSH decreased slightly during HD. We hypothesize that MDA may accumulate in ESRF due to reduced plasma clearance. Our results argue against a general increase of LPO in uremia.
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PMID:Influence of dialysis on plasma lipid peroxidation products and antioxidant levels. 888 87

A profound imbalance between oxidants and antioxidants has been suggested in uremic patients on maintenance hemodialysis. However, the respective influence of uremia and dialysis procedure has not been evaluated. Circulating levels of copper-zinc superoxide dismutase (CuZn SOD), glutathione peroxidase (GSH-Px), and reductase (GSSG-Rd), total GSH and GSSG were determined in a large cohort of 233 uremic patients including 185 undialyzed patients with mild to severe chronic renal failure, and 48 patients treated by peritoneal dialysis or hemodialysis. Compared to controls, erythrocyte GSH-Px and GSSG-Rd activities were significantly increased at the mild stage of chronic uremia (p < .001), whereas erythrocyte CuZn SOD activity was unchanged, total level of GSH and plasma GSH-Px activity were significantly decreased, and GSSG level and GSSG-Rd activity were unchanged. Positive Spearman rank correlations were observed between creatinine clearance and plasma levels of GSH-Px (r = .65, p < .001), selenium (r = .47, p < .001), and GSH (r = .41, p < .001). Alterations in antioxidant systems gradually increased with the degree of renal failure, further rose in patients on peritoneal dialysis and culminated in hemodialysis patients in whom an almost complete abolishment of GSH-Px activity was observed. In conclusion, such disturbances in antioxidant systems that occur from the early stage of chronic uremia and are exacerbated by dialysis provide additional evidence for a resulting oxidative stress that could contribute to the development of accelerated atherosclerosis and other long-term complications in uremic patients.
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PMID:Glutathione antioxidant system as a marker of oxidative stress in chronic renal failure. 890 30

At present, there are very few studies that look at the effect of uremia, prednisone and cyclosporine therapy on the lipid profiles of children. This effect is important because of the potential association of hyperlipidemia and increased risk of cardiovascular morbidity and mortality and glomerulosclerosis. We measured fasting lipid profiles in 73 children. There were 21 controls, 18 patients treated with cyclosporine and prednisone, 9 patients treated with cyclosporine alone and 25 dialysis patients. Lipoprotein (a) levels were measured using direct binding 'sandwich' ELISA. Uremic children had higher levels of triglycerides and very-low-density lipoprotein as compared with the control group. Children receiving combination of cyclosporine and prednisone also had higher total cholesterol, triglycerides, low-density lipoprotein, very-low-density lipoprotein as compared to the control group. However, children receiving cyclosporine monotherapy had lipid profiles similar to the control group. Patients receiving cyclosporine and prednisone had higher total cholesterol, high-density lipoprotein and low-density lipoprotein as compared with the dialysis group. Evaluating lipoprotein (a) levels, children on cyclosporine monotherapy had lower lipoprotein (a) levels as compared with children on dialysis and those receiving both combination therapy. The total cholesterol/high-density lipoprotein-cholesterol ratio (TC/HDL) was similar among the study groups. In summary, uremic children and children receiving steroids with cyclosporine have elevated lipid levels. However, the increased risk for atherosclerosis is not evident because of similar levels of lipoprotein (a) and TC/HDL ratios among the study groups.
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PMID:Hyperlipidemia in children: the role of uremia, steroids and cyclosporine therapy. 893 76

The macrophage scavenger receptor (SR) plays a leading role in atherogenesis, but little is known about the relevance of SR to atherosclerosis in uremia. In this study, the impact of uremic serum on SR expression and activity was examined in the human monocytic cell line U937. The cells were cultured with serum from ten healthy subjects, ten hemodialysis (HD) and ten continuous ambulatory peritoneal dialysis (CAPD) patients. SR mRNA expression was examined using reverse transcriptase-polymerase chain reaction followed by Southern blot. SR protein amount was evaluated by ligand blot. SR activity was analyzed by cellular uptake of fluorescently labeled acetylated low-density lipoprotein using flow cytometry. Uremic serum dose-dependently enhanced SR activity primarily by increasing the amount of receptor protein. Heat-inactivated uremic serum had a stimulatory effect, but ultrafiltrate of uremic serum, which included molecules with a molecular weight less than ten kDa, had no effect. The serum levels of macrophage-colony stimulating factor (M-CSF), an activator of SR, were fourfold higher in uremia and significantly correlated with SR activity in cells treated with uremic serum. Pre-treatment of uremic serum with a neutralizing antibody to M-CSF abolished the effect of uremic serum on SR activity. In conclusion, uremic serum contains a factor(s) that enhances SR expression and activity in U937 cells. Elevated M-CSF in uremic serum could be responsible for this enhancement.
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PMID:Uremic serum enhances scavenger receptor expression and activity in the human monocytic cell line U937. 906 11

Cardiovascular motality is high in patients with chronic renal failure treated with dialysis, and secondary hyperparathyroidism may promote atherosclerogenesis. Recent studies have revealed advanced atherosclerosis in hemodialysis patients by using high-resolution B-mode ultrasonography. Multiple regression analyses indicated that hyperphosphatemia and hyperparathyroidism were associated with increased intima-media thickness (IMT) of the carotid and femoral arteries in hemodialysis patients, respectively. Hypocalcemia and hyperparathyroidism independently and adversely affect the lipoprotein profile by suppressing hepatic triglyceride lipase (HTGL), a lipid-regulating enzyme playing important roles in the metabolism of intermediate density lipoprotein (IDL) and high density lipoprotein (HDL). Plasma IDL is raised markedly, and HDL is lowered in uremia. These lipoprotein changes are closely associated with increased aortic pulse wave velocity (PWV), an index of aortic sclerosis. These findings support the hypothesis that deranged calcium-phosphate homeostasis and secondary hyperparathyroidism promote atherosclerosis in uremia, at least partly by affecting lipoprotein metabolism. Adequate dialysis and efforts to normalize calcium, phosphate and PTH would be beneficial in preventing not only bone disease, but atherosclerosis as well.
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PMID:Atherosclerosis in uremia: possible roles of hyperparathyroidism and intermediate density lipoprotein accumulation. 935 Jun 91

Hyperhomocysteinemia has been shown to constitute an independent risk factor for premature occlusive arterial disease. Moderate hyperhomocysteinemia is present in chronic uremic patients, who often develop premature atherosclerosis, but no direct evidence of an association between the occurrence of atherosclerotic cardiovascular accidents (CVAs) and hyperhomocysteinemia has yet been reported in such patients. We serially determined total plasma homocysteine (Hcy) levels in a cohort of 93 consecutive chronic renal failure, undialyzed patients (57 males, 36 females) with creatinine clearance (Ccr) < 50 ml/min.1.73 m2 and age > or = 50 years at start of follow-up, together with serial assessment of Ccr and blood lipid parameters. From January 1989 to December 1995, 24 patients (group 1) experienced myocardial infarction (18 cases, 13 males) or cerebral infarction (6 cases, 3 males) while the remaining 69 (group 2) remained free of CVAs. Patients in groups 1 and 2 did not differ with respect to age (66 +/- 1.8 vs. 65 +/- 1.1 years, mean +/- Se) or serum creatinine (227 +/- 24 vs. 251 +/- 36 mumol/l) at onset of a CVA (group 1) or at the end of follow-up (group 2). The mean Hcy level was significantly higher in group 1 (20.7 +/- 1.6 vs. 12.8 +/- 0.5 mumol/l, p < 0.0001), as was the proportion of patients with Hcy in excess of 14 mumol/l, the upper limit in healthy controls (83 vs. 30%, p < 0.0001). Logistic regression analysis identified Hcy as an independent risk factor for CVA, with an odds ratio of 11.4 (95% confidence interval 3.5-37.7), which remained significant after adjustment on other variables. We conclude that an elevated Hcy level is associated with a risk of occlusive arterial accidents in patients with chronic renal failure and that hyperhomocysteinemia contributes to the accelerated atherosclerosis complicating chronic uremia.
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PMID:Hyperhomocysteinemia is associated with atherosclerotic occlusive arterial accidents in predialysis chronic renal failure patients. 938 10

To evaluate the metabolic effects of long-term treatment with recombinant human (rh) GH in short children with chronic renal failure (CRF), annual oral glucose tolerance tests (oGTT) during rhGH therapy for up to 5 y in 53 prepubertal children with CRF on conservative treatment, dialysis, and after renal transplantation were compared with that of 12 age-matched children treated with rhGH for idiopathic short stature. At the start of rhGH treatment, fasting values of glucose, insulin, glycosylated Hb A (HbA1C), triglycerides, cholesterol, glucose, and insulin responses during oGTT were significantly elevated in all patient groups compared with control subjects (p < 0.001). In the total population, fasting and 2-h postprandial glucose concentrations were inversely correlated with GFR and positively with age and methylprednisolone dosage in transplanted patients. Fasting insulin levels were positively correlated with body mass index and inversely with GFR. RhGH treatment was not associated with a change in fasting or stimulated glucose concentrations in any treatment group throughout the observation period. In contrast, serum insulin levels increased during the first treatment year in all groups, resulting in a more marked elevation of integrated insulin levels in transplant (1402 +/- 179 pM) and dialysis (1025 +/- 114 pM) patients compared with conservatively treated patients (829 +/- 94 pM), and control subjects (719 +/- 89 pM) (p < 0.01). Hyperinsulinemia persisted in all treatment groups for up to 5 y of follow-up. In conclusion, age, renal function, and obesity are the major independent predictors of glucose tolerance in children with CRF. Long-term rhGH treatment does not affect glucose tolerance, but aggravates the preexisting hyperinsulinemia in children with end-stage renal disease. In concert with the dyslipidemia of uremia, the rhGH-promoted hyperinsulinemia may contribute to the long-term risk for premature atherosclerosis in patients with childhood onset CRF.
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PMID:Metabolic effects of long-term growth hormone treatment in prepubertal children with chronic renal failure and after kidney transplantation. The German Study Group for Growth Hormone Treatment in Chronic Renal Failure. 947 86

Macrophage colony-stimulating factor (M-CSF) is critically involved in the survival, proliferation, and differentiation of cells of the mononuclear phagocyte system. These cells acquire specialized functions depending on the tissue in which they reside, suggesting that the development of mature phenotypes is determined by the cooperative effect of other growth factors, and also by the various biologically active isoforms of M-CSF which are differentially regulated. Alteration of M-CSF expression is associated with many pathologic processes, implying that the cells of the mononuclear phagocyte system are critical in maintaining the balance between health and disease in conditions such as infertility, osteopetrosis, osteoporosis, atherosclerosis, uremia, and Alzheimer's disease
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PMID:Update on the biologic effects of macrophage colony-stimulating factor. 966 57

Patients with renal diseases like nephrotic syndrome, chronic renal failure (uremia) and renal transplantation frequently present disturbances of lipid metabolisms, however their pathogenesis is partially understood. Moreover, cardiovascular diseases are responsible for many deaths in these patients. Although the effect of the dyslipidemias in the development of atherosclerosis in renal diseases is not clear, they probably play a role. Since actually the survival of these patients is substantial, it is important to manage them appropriately with regard to their dyslipidemias. This review will examine the pathogenesis and treatment of dyslipidemias in patients with nephrotic syndrome, chronic renal failure and renal transplantation.
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PMID:[Dyslipidemias in renal diseases: pathogenesis and treatment]. 967 3


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