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)

Earlier we have isolated from human plasma desialylated low density lipoproteins (dLDL) and showed that, first, dLDL induce cholesterol esters accumulation--the main process accompanying atherosclerosis development. Second, the process of lipoprotein desialylation took place in plasma, and, finally, sialic acids removed from LDL are transferred to other serum glycoconjugates. In this study we have isolated from human plasma an enzyme transferring sialic acid residues (trans-sialidase) by affinity chromatography and studied its donor and acceptor specificity. Isolated enzyme in the presence of saccharide-acceptor can remove sialic acids from different lipoproteins, glycoproteins (fetuin, transferrin), and gangliosides (GM3, GD3, GM1, GD1a, GD1b). Plasma enzyme translocates alpha2-6, alpha2-3 and to a lower extent alpha2-8 bonded sialic acids. Sialoglycoconjugates of human serum erythrocytes, serum lipoproteins, glycoproteins, and gangliosides can serve as donors of sialic acid for trans-sialidase. Desialylated lipoproteins, especially dLDL, are more preferable sialic acid acceptors. Transferred sialic acid is found to be alpha2-6, alpha2-3, and alpha2-8 connected.
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PMID:Human plasma trans-sialidase donor and acceptor specificity. 1222 90

Anorexia and protein malnutrition, occasionally associated with obesity, are frequently observed in peritoneal dialysis (PD) patients. Both are recognized risk factors for cardiovascular (CV) morbidity and mortality. Leptin is produced by adipocytes and regulates body-fat mass through a satiety central effect. Leptin accumulates in the uremic state. We analyzed the relationship between plasma leptin levels, nutritional status, obesity, CV risk factors, and atherosclerosis in PD patients. Leptin was determined using a polyclonal antibody [radioimmunoassay: Linco Research, St. Louis, MO, U.S.A.]. The normal range was 1-7.8 ng/mL. We studied 38 PD patients. Mean leptin levels were 59.1 +/- 57.5 ng/mL (elevated in 32 patients). Women (n = 21) showed higher leptin levels than did men (80.4 +/- 60 ng/mL vs. 32.3 +/- 43.3 ng/mL, p < 0.01), in spite of both groups having a similar body mass index (BMI). A statistically significant direct correlation was found between leptin and BMI (r = 0.7, p < 0.01) and triceps skin-fold measurement (r = 0.77, p < 0.01). Leptin levels and renal creatinine clearance (CCr) showed no significant correlation. Independent of BMI, higher leptin levels were associated with parameters considered to be CV risk factors (Framingham study), such as serum triglycerides < 150 mg/dL (n = 29) as compared with > 150 mg/dL (44.2 +/- 53.2 ng/mL vs. 80 +/- 58.4 ng/mL, p < 0.05), cholesterol < 250 mg/dL (n = 28) as compared with > 250 mg/dL, (50 +/- 55.6 mg/dL vs. 84.7 +/- 57.7 mg/dL, p < 0.05), uric acid < 7 mg/dL (n = 28) as compared with > 7 mg/dL (47 +/- 53.7 mg/dL vs. 93.1 +/- 56.6 mg/dL, p < 0.05), and the presence or lack of presence of left ventricular hypertrophy [68.8 +/- 60 (n = 30) vs. 29.5 +/- 23.7 (n = 5), p < 0.05]. The patients were classified into two groups according to a clinical atherosclerosis score (CAS). Nineteen patients had low CAS scores, and they showed higher plasma leptin values than did the other patients (82.4 +/- 65.7 ng/mL vs 35.8 +/- 36.6 ng/mL, p < 0.05). Twelve patients with anorexia had lower leptin values than did patients with normal appetite (19.2 +/- 15.8 ng/mL vs. 91.3 +/- 58.8 ng/mL, p < 0.001). In non obese patients (BMI < 25 and CCr < 3 mL/min, n = 14), leptin had a statistically significant direct linear correlation with markers of nutrition, including albumin (r = 0.63, p < 0.05), transferrin (r = 0.4, p < 0.05), cholesterol (r = 0.65, p < 0.05), and triglycerides (r = 0.6, p < 0.05). Finally, plasma leptin levels were notably increased in the PD population, indicating increased production (possibly by chronic hyperinsulinism), or uremic retention, or both. By multivariate analysis, we confirmed the association between leptin levels and sex, leptin and BMI, and leptin levels > 40 ng/mL and sex and LVH. All of those features suggest that plasma leptin levels could be considered a marker of CV risk and food intake in non obese PD patients without inflammation.
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PMID:Leptin as a marker of nutrition and cardiovascular risk in peritoneal dialysis patients. 1240 21

Epidemiologic and experimental data suggest that excess iron may contribute to the development of cardiovascular diseases (CVD). Because increased LDL cholesterol, decreased HDL cholesterol and alteration of systolic blood pressure (SBP) have all been implicated as risk factors for atherosclerosis and related CVD, the present study was designed to determine whether excess iron alters serum lipids and SBP in control and hypercholesterolemic rats. Female Fischer rats were divided into four groups. The control group (C) was fed the control diet, the CI group was fed the control diet and given iron dextran injections, the hypercholesterolemic group (H) was fed a 1 g/100 g cholesterol diet, and the HI group was fed the cholesterol diet and given iron dextran injections. The rats were fed the diets for 8 wk and iron dextran injections were given during wk 6 at doses of 10 mg/d for 5 d. Excess iron reduced (P < 0.01) plasma total cholesterol in rats fed the cholesterol diet (5.31 +/- 0.83 and 3.17 +/- 0.31 mmol/L for H and HI, respectively). Excess iron also resulted in a redistribution of cholesterol among the various lipoprotein fractions, with an increase (P < 0.01) in HDL cholesterol (0.56 +/- 0.12 and 0.85 +/- 0.16 mmol/L for H and HI, respectively) and a decrease (P < 0.01) in LDL cholesterol (4.49 +/- 0.77 and 2.09 +/- 0.26 mmol/L for H and HI, respectively). This redistribution also occurred in the rats fed the control diet. The treatments did not affect SBP or heart rate. The high cholesterol diet affected iron homeostasis; group H had lower transferrin saturation than group C (P < 0.01); group HI had a lower serum iron concentration than group CI but did not differ from group H (P < 0.05). Therefore, we conclude that if iron has any effect on CVD, it is not through its influence on serum lipids and blood pressure.
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PMID:Iron overload in hypercholesterolemic rats affects iron homeostasis and serum lipids but not blood pressure. 1251 60

Platelet-activating factor (PAF) is a potent phospholipid mediator involved in various disease states such as allergic asthma, atherosclerosis and psoriasis. The human PAF receptor (PAFR) is a member of the G protein-coupled receptor family. Following PAF stimulation, cells become rapidly desensitized; this refractory state can be maintained for hours and is dependent on PAFR phosphorylation, internalization, and down-regulation. In this report, we characterized ligand-induced, long term PAFR desensitization, and pathways leading to its degradation. Some GPCRs are known to be targeted to proteasomes for degradation while others traffic via the early/late endosomes toward lysosomes. Specific inhibitors of lysosomal proteases and inhibitors of the proteasome were effective in reducing the ligand-induced PAFR down-regulation by 40 and 25%, respectively, indicating the importance of receptor targeting to both lysosomes and proteasomes in long term cell desensitization to PAF. The effects of the proteasome and lysosomal protease inhibitors were additive and, together, completely blocked ligand-induced degradation of PAFR. Using dominant-negative Rab5 and 7 and colocalization of the PAFR with the early endosome autoantigen I (EEAI) or transferrin, we confirmed that ligand-induced PAFR down-regulation was Rab5/7-dependent and involved lysosomal degradation. In addition, we also demonstrated that PAFR was ubiquitinated in an agonist-independent manner. However, a dominant negative ubiquitin ligase (NCbl) reduced PAFR ubiquitination and inhibited ligand-induced but not basal receptor degradation. Our results indicate that PAFR degradation can occur via both the proteasome and lysosomal pathways and ligand-stimulated degradation is ubiquitin-dependent.
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PMID:Trafficking, ubiquitination, and down-regulation of the human platelet-activating factor receptor. 1450 Jul 26

The aim of studies was a comparison of dialysis adequacy, nutritional parameters, results of the peritoneal equilibration test (PET) and selected standard clinical and laboratory data in peritoneal dialysis (PD) patients with different age, but comparable PD duration and outcome. Two groups of patients were examined: group I (n = 21, 9 F, 12 M) - age 67.7 +/- 4.5 yrs, PD duration 20.1 +/- 12.1 months; group II (n = 21, 9 F, 12 M) - age 42.8 +/- 9.1 yrs, PD duration 20.7 +/- 12.1 months. Parameters of PD adequacy, results of PET, markers of nutrition and standard laboratory measures were determined every 3 months to the end of PD treatment. First obtained values, mean values representing the entire PD course and last values obtained before the end of PD therapy were compared in group I and II. Differences in results obtained at the beginning and at the end of PD therapy were also compared in each group. At the beginning of PD therapy the older patients showed higher total fat mass (TFM) expressed as % of total body mass (TBM), lower lean body mass (LBM), lower serum levels of iron, phosphorus and creatinine as well as lower transferrin saturation. When mean values representing the entire PD course were compared, the older patients showed higher TFM as % of TBM and serum ferritin level, whereas lower values were observed for diastolic blood pressure (DBP), LBM, serum creatinine, phosphorus and iron. At the end of PD therapy TFM as % of TBM and serum ferritin level remained higher in older patients as well as lower both DBP and LBM were maintained. Additionally, serum cholesterol level and residual renal function (RRF) became at the end of PD treatment higher in the older individuals compared to the younger ones. The difference in RRF between the two groups was caused by the decline in RRF in the younger patients with relatively stable values of RRF in the older ones. Nutritional parameters improved in the course of PD only in the younger group. In conclusion, the older patients reach similar PD outcome parameters compared to the younger ones while they show higher TFM as % of TBM, stable RRF and more satisfactory DBP. However, elderly patients show a greater progress in the deterioration of indices of both inflammation and atherosclerosis and therefore are not able to improve nutritional parameters.
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PMID:Possible factors contributing to similar peritoneal dialysis outcome in patients over 60 years of age and the younger ones. 1457 6

Endothelial dysfunction with atherosclerosis is a recognized complication of uremic patients. The hypoalbuminemia of peritoneal dialysis (PD) patients can induce a hypercoagulable and atherogenic state. In this study, we investigated the role played by malnutrition-inflammation syndrome on endothelial function markers in PD patients. We measured markers of nutrition [normalized protein catabolic rate (nPCR), albumin, prealbumin, insulin-like growth factor 1 (IGF-1), transferrin, and cholesterol], markers of endothelial damage and function [tissue-type plasminogen activator (tPA), thrombomodulin (TM), von Willebrand factor (vWF), and NO3 (representing NO)], markers of a coagulable state [fibrinogen and plasminogen activator inhibitor 1 (PAI-1)], markers of inflammation [tumor necrosis factor alpha (TNF alpha) and C-reactive protein (CRP)], and other endothelial injury factors [lipoprotein(a) [Lp(a)] and homocysteine]. We also performed an endothelial stimulation test consisting of right-arm venous occlusion (VO) for 10 minutes. The patients were divided into four groups according to their clinical atherosclerotic score (CAS). We studied 45 clinically stable PD patients. At baseline, statistically significant negative linear correlations were found between albumin and age (r = -0.54, p < 0.05), albumin and vWF post-VO (r = -0.54, p < 0.05), and albumin and TM (r = -0.36, p < 0.05), which are endothelial damage markers and prothrombotic factors. A positive linear correlation was seen between albumin and NO3 post-VO (r = 0.48, p < 0.05), indicating a high vasodilatation capacity. C-Reactive protein and TNF alpha showed a positive linear correlation (r = 0.5, p < 0.01). Similarly, TNF alpha showed a positive linear correlation with cardiovascular risk markers such as fibrinogen (r = 0.79, p < 0.01), PAI-1 (r = 0.44, p < 0.05), and homocysteine (r = 0.37, p < 0.05). Creatinine clearance showed a negative linear correlation with TM (r = -0.36, p < 0.05). Patients with albumin < 4 g/dL showed a lower tPA ratio, lower NO3, and a higher CRP, TNF alpha, and Lp(a) than did patients with albumin > 4 g/dL [tPA ratio: 2.1 +/- 1.56 (n = 29) vs. 2.6 +/- 2.3 (n = 16), p < 0.05; NO3: 47 +/- 27 micrograms/mL vs. 69 +/- 33 micrograms/mL, p < 0.05; CRP: 1.8 +/- 3 mg/dL vs. 1.1 +/- 1.6 mg/dL, p < 0.05; TNF alpha: 44.4 +/- 16 pg/mL vs. 36.6 +/- 21.4 pg/mL, p < 0.05; Lp(a): 55 +/- 39 mg/dL vs. 33 +/- 21 mg/dL, p < 0.05]. Patients with a worse CAS showed higher homocysteine levels and lower albumin values. Those relationships were maintained in both periods of the study. We found no relationships between dialysis dose and endothelial function markers. In conclusion, malnutrition-inflammation syndrome may contribute to endothelial dysfunction and, consequently, to prothrombotic and proatherogenic processes in PD patients.
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PMID:Malnutrition-inflammation syndrome is associated with endothelial dysfunction in peritoneal dialysis patients. 1476 71

Cardiovascular disease is common in patients with chronic kidney disease (CKD). As renal function fails, many patients become progressively malnourished, as evidenced by reduced levels of albumin, prealbumin, and transferrin. Malnourished patients have increased levels of C reactive protein (CRP), interleukin-6 (IL-6), and concomitant cardiovascular disease when they reach end stage. Many diseases that cause CKD, diabetes, and hypertension are also associated with cardiovascular disease. Thus the direct effect of renal failure per se directly contributing to the inflammation-malnutrition-atherosclerosis paradigm is not completely established in early stages of CKD. Some aspects of progressive renal failure, however, cause changes in plasma composition and endothelial structure and function that favor vascular injury. As renal function fails, hepatic apo A-I synthesis decreases and HDL levels fall. HDL is an important antioxidant and defends the endothelium from the effects of cytokines. Inflammation causes further structural and functional abnormalities in HDL. Apolipoprotein C III (apo C III), a competitive inhibitor of lipoprotein lipase is increased in CKD. Serum triglyceride levels increase as a result of accumulation of intermediate-density lipoprotein (IDL) comprising VLDL and chylomicron remnants. These impede vascular relaxation and are associated with cardiovascular disease. Activation of the renin angiotensin axis is a component of many renal diseases and adaptation to loss of renal mass. Angiotensin II (AngII) activates NADPH oxidases, leading to production of the superoxide anion and decreased availability of nitric oxide (NO), further impairing vascular function. H(2)O(2), produced as a consequence of superoxide dismutation, stimulates vascular cell proliferation and hypertrophy. Leukocyte-derived myeloperoxidase functions as an "NO Oxidase" in the inflamed vasculature and contributes to decreased NO bioavailability and compromised vascular reactivity. The changes in lipoprotein composition and structure as well as AngII-mediated alterations in endothelial function amplify the effect of subsequent inflammatory events.
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PMID:The role of oxidative stress-altered lipoprotein structure and function and microinflammation on cardiovascular risk in patients with minor renal dysfunction. 1497 55

Diabetes mellitus (DM) is a common disease affecting over 124 million individuals worldwide. DM is associated with high risk of atherosclerosis and renal, neural, and ocular damage. Increased oxidant stress has been implicated in the pathogenesis of DM. An increase in serum ceruloplasmin (Cp) levels has also been reported in Type 2 DM. Cp permits the incorporation of iron into transferrin (Trf). Trf inhibits iron ion-dependent OHo formation from H2O2. Patients with diabetes have increased levels of plasma lipid peroxidation products. In this study, we evaluated 50 patients with Type 2 DM and 21 clinically healthy subjects. Patients were divided into two groups. Group I included 29 patients without diabetic complications, Group II 21 with diabetic complications. Serum Cp, Trf, C-reactive protein (CRP), triglyceride (TG), cholesterol (Chol), and malondialdehyde (MDA) levels are studied. Serum Cp, CRP, TG, Chol, and MDA levels in diabetic patients were significantly higher than those of controls. Trf levels were significantly lower in diabetic patients than those of the controls. Cp, CRP, HbA1C, and MDA levels in Group II were significantly higher than those of Group I. Our results indicate that oxygen free radicals are formed in DM and can result in diabetic complications and that a prooxidant/oxidant imbalance is involved in the tissue injury in DM and diabetic complications.
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PMID:Levels of ceruloplasmin, transferrin, and lipid peroxidation in the serum of patients with Type 2 diabetes mellitus. 1520 35

Increasing evidence supports a role of cellular iron in the initiation and development of atherosclerosis. We and others reported earlier that iron-laden macrophages are associated with LDL oxidation, angiogenesis, nitric oxide production and apoptosis in atherosclerotic processes. Here we have further studied perturbed iron metabolism in macrophages, their interaction with lipoproteins and the origin of iron accumulation in human atheroma. In both early and advanced human atheroma lesions, hemoglobin and ferritin accumulation correlated with the macrophage-rich areas. Iron uptake into macrophages, via transferrin receptors or scavenger receptor-mediated erythrophagocytosis, increased cellular iron and accelerated ferritin synthesis at both mRNA and protein levels. The binding activity of iron regulatory proteins was enhanced by desferrioxamine (DFO) and decreased by hemin and iron compounds. Iron-laden macrophages exocytosed both iron and ferritin into the culture medium. Exposure to oxidized low-density lipoprotein (oxLDL, >or=50 microg/mL) resulted in <20% apoptosis of iron-laden human macrophages, but cells remained impermeable after a 24 h period and an increased excretion of ferritin could be observed by immunostaining techniques. Exposure to high-density lipoprotein (HDL) significantly decreased ferritin excretion from these cells. We conclude: (i) erythrophagocytosis and hemoglobin catabolism by macrophages contribute to ferritin accumulation in human atherosclerotic lesions and; (ii) iron uptake into macrophages leads to increased synthesis and secretion of ferritin; (iii) oxidized LDL and HDL have different effects on these processes.
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PMID:Secretion of ferritin by iron-laden macrophages and influence of lipoproteins. 1551 2

We had in view the effect of the oxidative aggression as determinant factor in atherogenic process associated with degenerative psychoorganic disturbances. It was studied a group of old people distributed in two subgroups: a) 51 old people with atherosclerosis (AS) and b) 57 old people with atherosclerosis associated with degenerative psychoorganic disturbances determined by chronic ethylism. The results were compared to those of a 40 healthy adults group. Concomitantly, it were evaluated the supervened modifications in the antioxidant defense systems of the organism, by determining both of some nonenzymatic defense system components (reduced glutathione, ceruloplasmine and transferrin) and of some enzymatic defense system components (superoxide dismutase, catalase and glutathione peroxidase). The obtained results emphasize an important aggression exerted by the lipid peroxides against the old people organism, aggression that is amplified by the chronic ethylism with appearance of the degenerative psychoorganic disturbances. Generally, the antioxidant defense capacity of the old people organism is depressed, especially in the group with atherosclerosis associated with degenerative psychoorganic disturbances engendered by excessive and chronic alcohol intake.
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PMID:Oxidative aggression in atherosclerosis associated to degenerative psychoorganic disturbances. 1552 47


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