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)

Remnants, resulting from the lipolysis of triglyceride-rich lipoproteins, injured cultured endothelial cells and resulted in decreased barrier function of the vascular endothelium. Endothelial cells were cultured on micropore filters. Albumin transfer across endothelial cell monolayers was measured after a 24-h exposure to media enriched with control or in vitro-lipolyzed samples of various hypertriglyceridemic (HTG) sera and its isolated lipoprotein (VLDL, LDL and HDL) and serum free protein (d greater than 1.21 g/ml) fractions. Compared with control cultures, neither control HTG serum nor its isolated lipoprotein and serum-free protein fractions had any effect on albumin transfer. In contrast, lipolyzed HTG (L-HTG) serum and all of its isolated lipoprotein fractions (L-VLDL, L-IDL, L-LDL and L-HDL) caused a marked decrease in endothelial barrier function, evidenced by a significant increase in albumin transfer across endothelial monolayers. The L-IDL and L-HDL fractions were more effective in increasing albumin transfer than the L-VLDL and L-LDL fractions. The extent of the L-IDL and L-HDL mediated increases in albumin transfer was concentration dependent. An exposure of 12 h was required for L-HDL to increase albumin transfer. The L-HDL mediated increase in albumin transfer was reversible only after a 12-h exposure at low concentrations. The free protein fraction from L-HTG serum had no significant effect on the barrier function of endothelial cells. The presence of normolipidemic HDL in culture medium prevented disruption of the endothelial barrier induced by L-IDL but not by L-HDL. The decrease in endothelial barrier function induced by lipolyzed samples of HTG serum or lipoproteins appeared to be correlated with the level of free fatty acids contained in lipolytic remnants. Enrichment of LDL, and in particular HDL, with fatty acid significantly increased albumin transfer. Compared with lipolyzed samples, sera/lipoproteins oxidized in vitro by Cu2+ ions had little effect on endothelial barrier function, which did not correlate with their respective thiobarbituric acid-reacting substance (TBARS) values. TBARS remained within normal range after L-HDL incubation with endothelial cells for up to 48 h. At most concentrations tested, exposure to lipolyzed but not oxidized lipoproteins resulted in morphological perturbations of cell monolayers. These data suggest that lipolytic remnants of triglyceride-rich lipoproteins may play an important role in the development of atherosclerosis by decreasing the barrier function of the vascular endothelium. The remnant-induced injury of the arterial wall may permit the entry of cholesterol-rich lipolytic remnants as well as LDL into the arterial wall.
Atherosclerosis 1992 Aug
PMID:Disruption of endothelial barrier function by lipolytic remnants of triglyceride-rich lipoproteins. 141 97

The relation between serum albumin levels and subsequent incidence of myocardial infarction and coronary heart disease deaths was evaluated using stored serum from the Multiple Risk Factor Intervention Trial (MRFIT). There were 91 coronary heart disease deaths, 113 myocardial infarction patients, and 405 controls matched to cases within 5 years of age, treatment group, and clinic site. There was a highly significant inverse relation between serum albumin level and risk of coronary heart disease. Individuals with a baseline level of serum albumin greater than or equal to 4.7 g/dl had an odds ratio of 0.45 as compared with individuals with a baseline level of serum albumin less than 4.4 g/dl. The relation persisted after adjusting for other cardiovascular risk factors (blood pressure, smoking, and serum cholesterol). The association was stronger for coronary heart disease deaths than for surviving myocardial infarction patients, and for cigarette smokers as compared with cigarette nonsmokers. The deaths studied occurred in the time period at least 6 years after the sera had been obtained and up to 10.5 years of follow-up, and the myocardial infarctions studied occurred within the first 6.5 years of follow-up. There was no consistent relation between time and death due to coronary heart disease or myocardial infarction and albumin levels. Albumin levels are related to the acute phase reaction. Lower albumin levels may be a marker of persistent injury to arteries and progression of atherosclerosis and thrombosis. The consistent relation between albumin and coronary heart disease risk requires further evaluation.
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PMID:The relation between serum albumin levels and risk of coronary heart disease in the Multiple Risk Factor Intervention Trial. 175 41

The stereoselective and saturable binding between receptor and ligand molecules plays an important role in many biological processes. Therefore ligand-receptor interactions have been increasingly studied in recent years by means of radionuclide labelled ligand molecules of high radiochemical purity and high specific activity. This contribution describes radiochemical development work of such radioligands performed at the Austrian Research Centre Seibersdorf in recent years: Tc99m-Neo-Galacto-Albumin was prepared as ligand for the Hepatic Binding Protein receptor, I-123-Low Density Lipoprotein (LDL) for LDL-receptors in the liver. Since LDL is involved in the origin of atherosclerosis it was subsequently labelled with Tc99m and In-111 as well. A pyrrolidine-methyl-benzamide derivative was separated into its stereoisomers and the active form labelled with I-123. It exhibited specific uptake in Dopamine D-2 receptor containing brain tissue. A benzazepine derivative was likewise labelled with I-123 as potential ligand for D-1 receptors.
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PMID:Recent developments in receptor binding radiopharmaceuticals. 192 70

The effects of dexamethasone (a synthetic glucocorticoid) and insulin on the secretion of very-low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) were investigated. Rat hepatocytes in monolayer culture were preincubated for 15 h in the presence or absence of combinations of 100 nM-dexamethasone and 2 nM-, 10 nM- or 50 nM-insulin. Dexamethasone increased [3H]oleate incorporation into secreted triacylglycerol by 2.7-fold and the mass of triacylglycerol secreted by 1.5-fold. Insulin alone decreased these parameters and antagonized the effect of dexamethasone. Dexamethasone increased the secretion of [3H]leucine in apolipoprotein (apo) E, and in the large (BH) and small (BI) forms of apo B in VLDL by about 7.1-, 3.6- and 4.0-fold respectively. Insulin alone decreased the secretion of these 3H-labelled apolipoproteins in VLDL. However, 2 nM-insulin with dexamethasone increased the secretion of 3H-labelled apo BH and apo BL by a further 0.8- and 3.2-fold respectively; 50 nM-insulin decreased the secretions of apo E, apo BH and apo BL in VLDL. Similar effects for dexamethasone or insulin alone were also obtained for the masses of apo E and apo BL + H secreted in VLDL. Albumin secretion was not significantly altered by either dexamethasone or insulin alone, but in combination they stimulated by 2.1-2.6-fold. Insulin or dexamethasone alone had little effect on the secretion of apolipoproteins in the HDL fraction. However, dexamethasone plus 2 nM-insulin increased the incorporation of [3H]leucine into apo AI, apo AH plus apo C, apo AIV and apo E of HDL by about 1.8-, 1.6-, 1.7- and 2.0-fold respectively. The apo E in the bottom fraction represented about 69% of the total 3H-labelled apo E secreted. The responses in the total secretion of apo E from the hepatocytes resembled those seen in HDL. The interactions of insulin and dexamethasone are discussed in relation to the general regulation of lipoprotein metabolism, the development of hyperlipidaemias and the predisposition to premature atherosclerosis.
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PMID:Stimulation of apolipoprotein secretion in very-low-density and high-density lipoproteins from cultured rat hepatocytes by dexamethasone. 224 66

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

The reactive vascular-injuring amino acid homocysteine was previously shown to be increased in plasma in diabetic patients with clinical signs of nephropathy. In this study, plasma homocysteine was measured in type 1 diabetic patients with normoalbuminuria (n = 22), microalbuminuria (n = 40) and proteinuria (n = 14) in order to investigate whether plasma homocysteine levels are increased already at the stage of incipient nephropathy, i.e. microalbuminuria. Furthermore, patients were characterized according to the degree of retinopathy. Plasma homocysteine in the whole population (n = 76) was related to B-Folate (r = 0.38, p < 0.01), S-Creatinine (r = 0.55, p < 0.001), S-Urea (r = 0.37, p < 0.01), U-Albumin (r = 0.46, p < 0.001), urinary N-acetyl-beta- glucosaminidase (r = 0.40, p < 0.001), systolic blood pressure (r = 0.36, p < 0.01) and diabetes duration (r = 0.44, p < 0.001). There were no differences in plasma homocysteine levels between patients with normoalbuminuria (8.0 +/- 1.7 mumol l-1; mean +/- SD) and those with microalbuminuria (9.1 +/- 3.4 mumol l-1). However, patients with clinical signs of nephropathy had higher plasma homocysteine levels (12.9 +/- 5.7 mumol l-1, p < 0.01) compared to the other two groups. There was no association between plasma homocysteine levels and different degrees of retinopathy. Thus, the present study does not show any relation between plasma homocysteine levels and early stages of diabetic nephropathy or retinopathy indicating that elevated concentrations of plasma homocysteine does not explain the increased risk for atherosclerosis observed in patients with microalbuminuria.
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PMID:Lack of association between plasma homocysteine levels and microangiopathy in type 1 diabetes mellitus. 770 67

Oxidation of low-density lipoprotein (LDL) may be important in the pathogenesis of atherosclerosis. We describe a method which measures the oxidation resistance of LDL isolated by a rapid procedure without added antioxidants. LDL was isolated from heparinized plasma by density gradient ultracentrifugation and desalted by gel filtration. The protein concentration was standardized to 50 mg/L and oxidation was promoted by copper (2 mumol/L) at 37 degrees C. The total sample preparation time was 2.5 h. Conjugated diene production was monitored at lambda = 234 nm with computation of the lag time. LDL oxidation was inhibited by EDTA but not heparin. Albumin inhibited LDL oxidation but only in concentrations greater than 50 mg/L. LDL was stable in frozen plasma (-70 degrees C) for 10 weeks, but unstable in the isolated and desalted state. The lag time for LDL from patients treated with the antioxidant probucol was markedly prolonged compared to normal subjects.
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PMID:A rapid method for measurement of the susceptibility to oxidation of low-density lipoprotein. 778 44

Oxidative modification of low-density lipoprotein (LDL) may play an important role in the initiation and progression of atherosclerosis. We previously showed that the cytotoxicity of oxidized LDL (oxLDL) depended on the level of lipid hydroperoxides. Meanwhile, it has been shown that during LDL oxidation, a significant part of the LDL phosphatidylcholine (PC) is degraded to lysophosphatidylcholine (LPC) by an intrinsic phospholipase A2-like activity, and that LPC is toxic to various cells. In the present study, we compared the toxicity of oxLDL with that of LPC in cultured bovine aortic endothelial cells. Cytotoxicity induced by LPC, assessed by the release of lactate dehydrogenase (LDH), reached a plateau within 1 h. LDH release induced by oxLDL occurred much later, at about 3 h, and increased linearly until nearly all the LDH was released at 10 h. The addition of deferoxamine, a Fe3+ chelator, to the reaction medium prevented the toxic effects of oxLDL, but not of LPC. Native LDL and oxLDL inhibited the toxicity of LPC, while native LDL promoted the toxicity of oxLDL. Albumin inhibited the toxicity of LPC but not of oxLDL. Preincubation of endothelial cells with an antioxidant, probucol, protected against oxLDL toxicity, but not against LPC toxicity. These results suggest that lipid hydroperoxides associated with the oxLDL particle, not LPC, constitute the toxic moiety of oxLDL. These substances may generate lipid peroxyl and alkoxyl radicals in the presence of ionic iron, probably from intracellular iron stores in endothelial cells, and produce cytotoxicity.
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PMID:Comparative toxicity of oxidatively modified low-density lipoprotein and lysophosphatidylcholine in cultured vascular endothelial cells. 796 Dec 95

Lipid accumulation in the human aorta occurs predominantly downstream of branches in foetuses, neonates and infants but upstream at later ages. The lipid in these deposits may derive from plasma lipoproteins. We have examined uptake of plasma proteins by the rabbit aortic wall near branches as a function of age. Albumin was labelled with a fluorescent dye and introduced into the circulation of animals fed a normal diet. The aorta was fixed in situ 3 h later and the distribution of tracer in sections through the wall was measured by using digital imaging fluorescence microscopy. Net uptake by the intima-media was higher downstream of intercostal ostia than upstream in young animals but this difference decreased and then reversed with age. Furthermore, the average of uptake by both regions was higher shortly after weaning than at later ages. These age-related variations in transport properties may explain discrepancies between previous studies of uptake, resolve apparent inconsistencies between the properties of rabbit and human arteries and, if applicable to man, might account for the non-uniform and changing pattern of lipid accumulation around arterial branches.
Atherosclerosis 1994 Mar
PMID:Age-related variations in transport properties of the rabbit arterial wall near branches. 801 1

Diabetes mellitus is known as an independent risk factor in atherosclerosis. Among the prominent biochemical changes that occur in diabetic state, are the enhanced formation of advanced glycosylation end products (AGE) (especially linked to albumin and collagen) and the impaired oxidative-antioxidative balance. Previously, we have shown that AGE-albumin (AGE-Alb) significantly alters the physico-chemical characteristics of low density lipoproteins of normal (nLDL) and diabetic (dLDL) subjects. In this study we tried to establish if incubation of nLDL or dLDL, with AGE-Alb in autoxidative conditions, modifies the rate and/or the pathway of their uptake by macrophages. To this purpose, nLDL and dLDL were exposed to AGE-Alb, and after re-isolation and radiolabeling the lipoproteins were incubated with U937 or peritoneal macrophages (for various time and concentrations), in the absence or presence of different competitors (native LDL, acetylated LDL, AGE-Alb, mannan) or cytochalasin D. As controls, nLDL and dLDL, maintained in similar conditions, but without AGE-Alb, were used. The results showed that preincubation for 24 h and 72 h with AGE-Alb augmented the macrophage uptake for both nLDL and dLDL (1.7-fold). Either pre-incubated or not with AGE-Alb, dLDL was taken up at a constantly higher rate than nLDL; the difference appeared more prominent at 72 h (1.5 vs. 4 micrograms LDL protein/mg cell protein). The increased level of glycation of native dLDL as compared to native nLDL (266 +/- 35 vs. 160 +/- 24 mmol HMF/mol apoB) as well as of the lipid peroxides (1.34 +/- 0.47 vs. 0.3 +/- 0.09 nmol MDA/mg apoB) could account for the greater uptake of dLDL at any preincubation time. Competition experiments indicated that, generally, incubation with AGE-Alb diminished the apo B100,E receptor-mediated uptake in favour of 'scavenger' receptor pathway and phagocytosis. Macrophage uptake of AGE-Alb modified dLDL was reduced approximately 30% by native nLDL, approximately 70% by acetylated LDL and approximately 38% by cytochalasin D. Together, these data suggest that the consequence of the alterations induced by AGE-Albumin on LDL is the increased macrophage uptake, via non-saturable pathways, that ultimately may lead to accelerated formation of atherosclerotic plaques in diabetics.
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PMID:Increased macrophage uptake of irreversibly glycated albumin modified-low density lipoproteins of normal and diabetic subjects is mediated by non-saturable mechanisms. 887 21


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