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)

Uptake of cholesterol-containing lipoproteins by macrophages in the arterial intima is believed to be an important step in the pathogenesis of atherosclerosis. There are a number of possible mechanisms by which macrophages might accumulate cholesterol, and one that has attracted much interest recently involves the uptake of oxidatively modified low density lipoprotein (LDL) via a specific cell surface receptor, termed the scavenger or acetyl-LDL receptor. Previous studies have shown that chemical derivatization of LDL with reagents that result in neutralization of the charge of lysine amino groups also allows recognition by this receptor. As well, it has been shown that oxidation of LDL is accompanied by a decrease in free lysine groups and binding of lipid products to apolipoprotein B. The present studies were done to further characterize the receptor-binding domain on oxidized LDL. It was found that LDL could be modified by incubation with water-soluble products derived from autoxidized unsaturated fatty acids under conditions that inhibited oxidation of the LDL itself. The LDL modified in this way had increased electrophoretic mobility but showed no evidence of the oxidative damage that typifies LDL oxidized by exposure to metal ions. Furthermore, the oxidation product-modified LDL was rapidly degraded by cultured macrophages through the scavenger receptor pathway. Bovine albumin modified by oxidation products also showed greatly accelerated degradation by macrophages. When analyzed by reverse-phase high pressure liquid chromatography, the reactive oxidation products appeared less polar than fatty acids or simple medium-chain aldehydes. When treated with the carbonyl reagent 2,4-dinitrophenylhydrazine, the reactive fractions yielded derivatives, some of which were identified by mass spectrometry as hydrazones of nonenal, heptenal, pentenal, and crotonaldehyde. A series of 2-unsaturated aldehydes (acrolein to 2-nonenal) were all found to modify LDL, but none of these aldehyde-modified LDLs were recognized by the scavenger receptor of macrophages and all were degraded much more slowly by these cells than LDL modified with oxidation products. Furthermore, copper-oxidized LDL had only very slight immunoreactivity toward a panel of antibodies specific for adducts of simple 2-unsaturated aldehydes. Analysis of underivatized autoxidized fatty acids by coupled liquid chromatography/thermospray mass spectrometry revealed compounds with m/z corresponding to M+17, M+31, and 2M+31 in fractions that were capable of modifying LDL. The unoxidized fatty acids showed a dominant peak at M-1. These results indicate that the scavenger receptor of macrophages can recogn
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PMID:Recognition of oxidized low density lipoprotein by the scavenger receptor of macrophages results from derivatization of apolipoprotein B by products of fatty acid peroxidation. 276 57

Lecithin:cholesterol acyltransferase (LCAT) and lysolecithin acyltransferase (LAT) are two activities carried out by the same plasma enzyme, but require different apoprotein activators. The LCAT reaction takes place primarily on high density lipoproteins (HDL) and is activated by serum albumin, whereas LAT takes place on low density lipoproteins (LDL) and is inhibited by albumin. In nephrotic syndrome (NS), the levels of serum albumin are reduced, whereas the LDL levels are increased, and therefore, the ratio of LAT/LCAT activities should be increased. To test this hypothesis, we estimated the lipid levels and the two enzyme activities in experimental NS induced in rats by the injection of anti-Fx1A antibody (passive Heymann nephritis). As found in other nephrotic conditions, the plasma lipid levels rose progressively as the proteinuria increased and the serum albumin concentration declined. In addition, the ratio of LAT/LCAT activities increased by about fourfold after nine days of induction of nephritis. The LCAT activity correlated positively and the LAT activity negatively with serum albumin levels. The esterified cholesterol correlated positively with LCAT activity in normal rats but negatively in nephrotic animals, indicating that most of the cholesteryl esters in NS may be non-LCAT derived. The free cholesterol/lecithin ratio, a known risk factor for atherosclerosis, increased significantly in nephrotic rats. Furthermore, since the increase in the LAT activity produces more disaturated lecithins, another putative risk factor, the cumulative risk of coronary heart disease may be increased in long-term NS.
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PMID:Plasma lipids and acyltransferase activities in experimental nephrotic syndrome. 277 94

This study measured endothelial permeability, quantitatively (with iodine 125-labeled albumin) and qualitatively (with Evans blue dye) in arterialized vein grafts in 9 adult dogs. In each dog, the right common carotid artery was ligated and arterial flow was reconstituted with a 5-cm bypass graft of right external jugular vein. Twenty-four hours before the dogs were killed, each dog received both 125I-labeled albumin (8 microCi/kg) and Evans blue dye (15 mg/kg) intravenously. After the dogs' death, each arterialized vein graft and each left external jugular vein (as control) was harvested and studied. Arterialized vein graft permeability was significantly increased over control at 1, 3, and 6 months (3 dogs at each interval). Scanning electron microscopy revealed confluent endothelium in all specimens. This increased permeability may play a role in vein graft atherosclerosis.
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PMID:Evaluation of arterialized vein graft permeability with Evans blue dye and iodine 125-labeled albumin. 224 63

Recent dietary recommendations for patients with diabetes mellitus have focussed on the liberalisation of carbohydrate intake to at least 50% of total calories. However, there are reports that this diet may cause adverse metabolic effects as a result of high intake of carbohydrate. Whether this high-carbohydrate diet will exacerbate hypertriglyceridaemia, which increases the risk of atherosclerosis, and diabetic microalbuminuria, which predisposes to progressive renal failure, is unknown. The dietary intake of 28 patients with insulin-dependent diabetes mellitus was assessed by diet histories with both questionnaire surveys and 3-day recall methods. The dietary contents of different constituents were graded according to the type and amount of food typically eaten, and the frequency of their consumption in the past 6 months. Twelve patients were found to have a high dietary intake of carbohydrate and this was confirmed by detailed assessment of food intake records over a 3-day period. The carbohydrate intake of these 12 patients amounted to at least 55% of total calories. Total calorie intake, body weight, mean blood pressure, glycaemic control, and glomerular filtration rate were similar between the 12 patients with high intake of carbohydrate and the other 16 patients with low intake. Urinary protein and albumin appearance as measured by dye binding and immunoassay, fasting cholesterol, triglyceride and high-density lipoprotein cholesterol were also comparable between the two groups. This study provides evidence that a high-carbohydrate diet in the treatment of diabetes mellitus is not associated with significant alterations in the amount of microalbuminuria or in hypertriglyceridaemia.
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PMID:Effects of diets with high carbohydrate content on diabetic hyperlipidaemia and microalbuminuria. 284 37

Atherosclerosis is characterized by focal areas of lipid accumulation and intimal smooth muscle cell proliferation in large arteries. In vivo studies on rat aorta with Evans blue-albumin conjugate (EBA) have shown that there are preferential sites of increased permeability with an increased uptake of the conjugate. It has been shown that these blue areas are associated with a high endothelial cell turnover rate and an enhanced permeability to lipids. In a previous study, we demonstrated that 99% of endothelial cells in the mitotic (M) phase as identified by hematoxylin staining of the dividing nuclei exhibited EBA leakage and that these dividing cells accounted for 30% of all leakage sites. In the present study, experiments were performed on the thoracic aortas of 10 adult male Sprague-Dawley rats to determine the statistical frequency of isolated leaks to Lucifer yellow-low density lipoprotein conjugate (LY-LDL) at the level of individual cells and to assess the relationship of such leaks to the cell turnover processes. Leakage of LY-LDL around individual endothelial cells was visualized by fluorescence microscopy, and cells in mitosis on the same specimens were identified by hematoxylin staining. Although endothelial cell mitosis is infrequent (0.034%), 80% of dividing cells in the M phase were associated with LY-LDL leakage. These dividing cells accounted for 45% of all leakage spots. These findings lend support to our recent hypothesis that transiently open junctions surrounding the endothelial cells undergoing cell turnover provide pathways through which LDL enters the subendothelial space, resulting in lipid accumulation.
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PMID:Transendothelial transport of low density lipoprotein in association with cell mitosis in rat aorta. 292 79

Lipoprotein(a) has been shown to be an independent risk factor for atherosclerosis. The effect of different forms of plasmapheresis therapy on the removal of Lp(a) is examined. Plasmapheresis is successfully administered in a small number of hypercholesteremic patients who fail to respond to conventional therapy. Comparison of four different methods of plasma exchange (albumin substitution, anti-apoB antibody column, LDL precipitation, filtration) reveals significant differences in effectiveness in the ability to lower plasma Lp(a): plasma exchange with albumin und LDL precipitation seem to be the most effective, plasma filtration the least.
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PMID:Reduction of Lp(a) by different methods of plasma exchange. 297 58

Isolation of non-esterified [14C]cholesterol bound to albumin from rat serum, 8 days after i.p. injection of [14C]cholesterol, was achieved by affinity chromatography, using Cibacron blue F3GA bound to Sepharose 4B and by Sephadex G-150 column chromatography. Both methods permit isolation of large quantities of cholesterol-loaded albumin, free of globulins and lipoproteins. The isolated albumin-cholesterol fraction was estimated to be 4.6 mg/100 ml serum, which represents approx. the 24% of the non-esterified cholesterol present in the rat serum. Albumin-cholesterol, cholesterol glucoside, cholesterol hemisuccinate and hydroxylated derivatives of cholesterol produced a biphasic curve of changes in synaptosomal plasma membranes (SPM)-bound (Na+ + K+)-stimulated ATPase activity. Low concentrations of the ligand progressively increased the enzyme activity, while increasing the ligand concentration above that which maximally stimulated the enzyme activity, produced a progressive inhibition. Lipoproteins did not have any effect on the enzyme activity. The fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene-labeled SPM, increased in albumin-cholesterol derivatives-treated SPM, which is consistent with a general decrease in membrane bilayer fluidity. The results provide evidence that the 'albumin-cholesterol' fraction of the serum may directly affect the cell membrane-bound enzyme activity.
Atherosclerosis 1986 Jul
PMID:Evidence for the existence of non-esterified cholesterol carried by albumin in rat serum. 301 57

Patients with insulin dependent diabetes mellitus who develop proteinuria may die prematurely, whereas those who do not develop this complication have a comparatively normal life span. The excess mortality in diabetics with proteinuria is from cardiovascular as well as renal disease, but the reason is unclear. Risk factors for vascular disease were therefore assessed in 22 insulin dependent diabetics with proteinuria, but not renal failure, who were matched for sex, age, duration of diabetes, and glycated haemoglobin (HbA1) values with a similar number who had normal urinary albumin excretion rates. Macrovascular disease (ischaemic heart disease and peripheral vascular disease) was present in 10 patients with proteinuria but in only three with normal albumin excretion rates, and proliferative retinopathy was detected in 11 and four patients in the two groups. There was no significant excess of smokers in the group with proteinuria. Blood pressure was, however, higher in the patients with proteinuria--mean systolic pressure 161 (SD 18) mm Hg compared with 135 (19) mm Hg (95% confidence interval of difference between means 15 to 38 mm Hg); mean diastolic pressure 90 (SD 12) mm Hg compared with 79 (15) mm Hg (confidence interval 3 to 19 mm Hg). The concentration of serum high density lipoprotein (HDL) cholesterol isolated by precipitation was lower in the patients with proteinuria (confidence interval 0.02 to 0.41 mmol/l). Their concentration of HDL2 cholesterol isolated by ultracentrifugation was also decreased (confidence interval 0.02 to 0.40 mmol/l), whereas HDL3 cholesterol tended to be increased (confidence interval -0.01 to 0.23 mmol/l). There was also a trend for serum cholesterol concentrations to be higher in the presence of proteinuria (confidence interval -0.39 to 1.20 mmol/l). The aggregation of risk factors for atherosclerosis in insulin dependent diabetes mellitus complicated by proteinuria helps to explain the increased prevalence of ischaemic heart disease and peripheral vascular disease reported in these patients. Early renal disease in insulin dependent diabetes may have an important role in hypertension and altered lipoprotein metabolism.
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PMID:Influence of proteinuria on vascular disease, blood pressure, and lipoproteins in insulin dependent diabetes mellitus. 311 68

Cultured rat hepatocytes were used to study the effects of hormones on the production of apo A-I. In addition, we compared these effects with the production of albumin. Hepatocytes were isolated from normal adult rat livers and cultured in MEM, as nearly confluent monolayers. In the absence of hormones, apo A-I and albumin accumulated in the culture medium almost linearly for periods up to 24 h. The rates of accumulation of apo A-I and albumin in the medium were 22 ng/mg cell protein per h and 1.2 micrograms/mg cell protein per h, respectively. During the incubations the cellular contents of apo A-I remained constant. Insulin stimulated the production of albumin at concentrations over 10(-10) M, but inhibited the production of apo A-I at concentrations over 10(-8) M. Dexamethasone showed no significant effects on albumin production but stimulated apo A-I production at concentrations over 10(-6) M. Glucagon inhibited the production of albumin and apo A-I dose-dependently at concentrations over 10(-10) M. Thus, the production of albumin and apo A-I are presumably controlled by different regulatory mechanisms.
Atherosclerosis 1988 Apr
PMID:Effects of insulin, dexamethasone and glucagon on the production of apolipoprotein A-I in cultured rat hepatocytes. 313 65

Phospholipids in high density lipoproteins (HDL) is being used as a negative risk indicator of atherosclerosis. Phospholipids in HDL may not demonstrate the actual level of HDL-phospholipids when determined by the precipitation or ultracentrifugal methods, because HDL fractions contain very high density lipoproteins (VHDL) and albumin. In the present study, the true level of phospholipids in HDL was estimated using high performance liquid chromatography (HPLC), and it was compared with the level of phospholipids in HDL determined by the precipitation method. Sera from 18 healthy subjects were used as materials. In the HPLC method, the HDL fraction was extracted making sure that it contained no free albumin, which is albumin not bound to phospholipids. The HDL fraction was separated into subfractions. It was found that phospholipids in the VHDL fraction make a 20.2 +/- 7.3% (mean +/- S.D.) part of the total HDL-phospholipids. A large part of the VHDL fraction was constituted of albumin-bound phospholipids. A significant correlation was observed between HDL-phospholipids determined by the precipitation method, which contain albumin, and the actual HDL fraction phospholipids determined by HPLC, which do not contain VHDL (r = 0.903, p less than 0.01). These results suggest that HDL-phospholipids values determined by the precipitation method give useful clinical data.
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PMID:An evaluation of serum high density lipoproteins-phospholipids. 317 21


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