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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The concentrations of plasma proteins of different molecular weights were measured in layers across the human aortic wall. On a volumetric basis the concentration of low density lipoprotein (LDL) in inner intima, adjacent to the endothelium, was almost twice the concentration in the patient's plasma. With the exception of transferrin, which behaved anomalously, the concentration of each protein was a linear function of is plasma concentration and molecular weight, so that the relative retention of albumin was only 15% of LDL retention and its concentration in inner intima less than one-quarter of the plasma concentration. Between the inner (luminal) and outer layers of intima the concentration of all proteins decreased by about 40%. In aortas in which the internal elastic lamina (IEL) appeared to be intact it provided an almost total barrier to LDL, but for smaller proteins the concentrations in the layer immediately outside it were inversely related to molecular weight; the concentration of LDL was only 0.3% of the intimal concentration whereas albumin was 26% of the intimal concentration. However, in aortas in which the IEL appeared morphologically frayed, fragmented or discontinuous there was an 80% increase in albumin, and a 25-fold increase in LDL in this layer. The differential barrier functions of endothelium and IEL produce bizarrely different macromolecular environments for smooth muscle cells in intima and media.
Atherosclerosis 1980 Dec
PMID:Distribution of plasma proteins across the human aortic wall--barrier functions of endothelium and internal elastic lamina. 616 19

Modifications of plasma lipoprotein structure and function resulting from in vivo post-translational nonenzymatic glycosylation may play a role in the premature atherosclerosis of patients with diabetes mellitus. This report describes the generation and characterization of six unique murine monoclonal antibodies that bind glucosylated human plasma lipoproteins, but do not react with normal plasma lipoproteins. This was accomplished by immunizing mice with homologous glucosylated low density lipoprotein. In competitive inhibition radioimmunoassays, the dominant epitope recognized by these antibodies on glucosylated low density lipoprotein was identified as glucitollysine, the reduced hexose alcohol form of glucose conjugated to the epsilon amino group of lysine. Each of these antibodies was capable of identifying glucitollysine epitopes on all reduced glucosylated proteins studied, including high density lipoprotein, albumin, hemoglobin, and transferrin. These antibodies were also capable of identifying and quantitating glucitollysine residues on the total plasma proteins and isolated lipoproteins of normal and diabetic individuals after reduction of the proteins with NaBH4. Preliminary data suggest that diabetic total plasma proteins and isolated lipoproteins contain at least threefold more immunochemically detectable glucitollysine residues than nondiabetic plasma proteins and lipoproteins. The technique described in this report should allow production of region-specific antibodies to any immunogenic modification of a protein.
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PMID:A novel method for generating region-specific monoclonal antibodies to modified proteins. Application to the identification of human glucosylated low density lipoproteins. 641 10

Atherosclerotic lesions contain multiple cell types including smooth muscle cells, macrophages, and T lymphocytes. The development of an extralymphatic T lymphocyte focus of inflammation in this condition requires chemoattractant-induced cell migration and growth factor-induced cell activation. In a previous study, we described a novel 13-15-kDa T lymphocyte-specific chemotactic cytokine, endothelial cell-derived lymphocyte chemoattractant activity (ED-LCA), secreted by serotonin-stimulated bovine aortic endothelial cells that is distinct from previously identified endothelial cell-derived interleukins (IL) 1, 6, and 8. Because of the association between T lymphocyte chemotactic and growth factor activity, in the current study we investigated the effect of ED-LCA on T cell growth. We assessed its capacity to induce markers of the passage of T cells from the resting (G0) state into the G1 phase of the cell cycle, such as receptors for IL-2 (IL-2R) and transferrin (TFR) and class II major histocompatibility complex antigens (HLA-DR). Incubation of G0 freshly isolated human T lymphocytes for 48 h with chromatographically resolved, partially purified ED-LCA resulted in a threefold increase in expression of the p55 subunit of IL-2R, a threefold increase in TFR, and a twofold increase in HLA-DR. Passage into the G1 phase of the cell cycle was confirmed by cell cycle analysis employing acridine orange. Evaluation of CD4+ and CD8+ T cell subsets by double-antibody labeling demonstrated that the p55 subunit of IL-2R was induced in both T cell subsets. Although incubation of human T cells with ED-LCA alone did not induce proliferation, addition of exogenous IL-2 to T cells pulsed with ED-LCA for 24 h caused a proliferative response with a stimulation index of 3. By up-regulating functional cell surface receptors for IL-2, ED-LCA is a competence growth factor for T lymphocytes and primes them to respond to IL-2. By virtue of its effect on T cells, as a chemotactic and competence factor, this endothelial cell-derived mitoattractant could participate with other T cell growth factors like IL-2 in the recruitment and amplification of the extralymphatic T cell component of atherosclerosis.
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PMID:Serotonin-stimulated aortic endothelial cells secrete a novel T lymphocyte chemotactic and growth factor. 751 99

A chondroitin sulfate-dermatan sulfate proteoglycan was isolated from bovine aorta intima by extraction of the tissue with 4 M guanidine hydrochloride. The proteoglycan was purified by CsCl isopycnic centrifugation followed by gel filtration and ion exchange chromatography. A monoclonal antibody C8F4 was developed to this core protein. The characteristics and specificity of the antibody were studied by an enzyme-linked immunosorbent assay (ELISA) using an alkaline phosphatase conjugated antibody (goat anti-mouse IgG). The antibody binding to the core protein was found specific and optimal at pH 7.0. The antibody recognizes either intact chondroitin sulfate-dermatan sulfate proteoglycan monomer, chondroitinase ABC digested monomer or chemically deglycosylated proteoglycan. Free chondroitin sulfates, keratan sulfate and hyaluronic acid did not compete for the antigenic sites in ELISA. Limited hydrolysis of the core protein by trypsin resulted in three peptides and only the peptide with a molecular weight M(r) = 40,000 was found capable of binding to hyaluronic acid. The antibody C8F4 recognized this hyaluronic acid binding peptide but did not recognize the other two peptides suggesting that the epitope(s) for this antibody is in the hyaluronic acid-binding region of the core protein. The antibody recognized the core proteins from bovine nasal cartilage proteoglycan and human aorta proteoglycan but did not recognize bovine aorta link protein, bovine serum albumin, human serum albumin, human transferrin, collagen Type I and fibronectin. The antibody was found useful to localize proteoglycans in atherosclerotic lesions in human aorta by immunohistochemical techniques.
Atherosclerosis 1993 Jan 25
PMID:A monoclonal antibody that recognizes hyaluronic acid binding region of aorta proteoglycans. 768 Dec 90

Low density lipoprotein (LDL) oxidation within the arterial wall may contribute to the disease of atherosclerosis. We have investigated the conditions under which transferrin (the major iron-carrying protein in plasma) may release iron ions to catalyse the oxidation of LDL. Transferrin that had been incubated at pH 5.5 released approximately 10% of its bound iron in 24 h, as measured by ultrafiltration and atomic absorption spectroscopy. Furthermore, transferrin co-incubated with LDL and L-cysteine at pH 5.5 resulted in the oxidation of the LDL as measured by thiobarbituric acid-reactive substances and electrophoretic mobility. This effect was observed at transferrin concentrations as low as 40% of its average plasma concentration. The release of iron from transferrin in atherosclerotic lesions due to a localised acidic pH may help to explain why LDL oxidation occurs in these lesions.
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PMID:Iron released from transferrin at acidic pH can catalyse the oxidation of low density lipoprotein. 792 32

High body iron stores have been proposed as a risk factor for advanced atherosclerosis. We investigated the prevalence of early atherosclerotic changes, and their relation to conventional CHD risk factors and body iron status. A cross-sectional study was carried out in 206 men aged 50 to 60 years (6% random population sample). Intima-media thickness (IMT) of the carotid artery was evaluated with high-resolution B-mode ultrasonography. Statistical analyses were performed separately for men with and without cardiovascular disease (CVD). Among all the study participants, 6.6% had IMT > 1.3 mm in the common carotid artery, whereas 53.8% had IMT > 1.5 mm in the carotid bifurcation. Respective values were 4.8% and 46.8% for those without CVD, and 8.5% and 62.2% for those with CVD. Mean IMT in the carotid bifurcation, the predilection site for atherosclerosis, was 1.85 mm (95% CI 1.72; 1.98) in the men with CVD, as compared to 1.65 mm (95% CI 1.56; 1.73) in the men free of CVD. Serum LDL cholesterol (beta = 0.26), saturated fat intake (beta = 0.20), blood haemoglobin (beta = -0.29), systolic blood pressure (beta = 0.21) and smoking (beta = 0.19), jointly explained 23% of the variance in the carotid bifurcation IMT in the men without CVD. Neither serum ferritin, transferrin nor dietary iron levels were associated with carotid bifurcation atherosclerosis. On the other hand, in the men with CVD, age (beta = 0.34) and physical activity (beta = -0.25) jointly explained 16.5% of the IMT variance in the carotid bifurcation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Association of risk factors and body iron status to carotid atherosclerosis in middle-aged eastern Finnish men. 798 92

This study evaluated the effect of dietary cadmium (Cd) on atherosclerosis in the rabbit. Cholesterol was added to the diet to initiate and/or accelerate atherogenesis. Cd was added to the diet at two dose levels. Uptake of Cd was 55 micro gram/kg body weight (BW)/day at the low dose level and 1350 micrograms/ kg BW/day at the high dose level. Five groups of rabbits were fed five different diets for 9 months: (1) basal diet without additional constituents; (2) background diet, which was basal diet to which cholesterol had been added; (3) the low-dose level Cd diet, which was background diet to which 2 mg Cd/kg had been added; (4) high-dose level Cd diet, which was background diet to which 50 mg Cd/kg had been added; and (5) basal diet to which 50 mg Cd/kg had been added. Dietary cholesterol increased blood total leucocyte count, serum and liver total cholesterol concentrations, serum total bilirubin concentration, low-density lipoprotein vitamin E concentration and induction of atherosclerotic plaques in the aorta and coronary arteries. Cd in the diet increased liver and kidney Cd concentrations in a dose-dependent way, decreased prothrombin time and temporarily increased urea and creatinine clearances. Slight kidney damage was induced by Cd only in animals fed the high-dose level Cd diet (with or without cholesterol). Dietary Cd partly counteracted the dietary cholesterol-induced increases of serum and liver total cholesterol concentrations, and tended to reduce plaque formation in the aorta. Dietary Cd in rabbits fed cholesterol-containing diets influenced cholesterol metabolism and tended to decrease atherosclerosis in a dose-related fashion. This is in contrast with limited epidemiological human data. Dietary Cd also decreased serum ferritin concentration and increased serum transferrin concentration. Free iron concentration is associated with myocardial infarction in man and augments the development of atherosclerosis in rabbits. It is concluded that the observed reduction in atherogenesis is related to dietary Cd-induced changes in cholesterol metabolism, increased rheology of blood and/or, most likely, reduced free iron concentration.
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PMID:Cadmium and atherosclerosis in the rabbit: reduced atherogenesis by superseding of iron? 876 54

Free Iron, as well as other transition metals, can catalyze free radical formation. For this reason iron is tightly bound to transport and storage proteins to prevent their involvement in free radical formation. It has been hypothesized that increased iron intake or iron stores may promote atherogenesis by increasing free radical formation and oxidative stress. While a coherent, plausible hypothesis as to how transition metals, such as iron, might accelerate the progression of atherosclerosis has been generated from basic research, iron status, measured as dietary iron intake, serum iron, serum ferritin, and transferrin saturation, has been inconsistently associated with cardiovascular disease in human epidemiologic research. In addition, limited data suggest that iron overload states do not appear to be strongly associated with increased risk of atherosclerotic disease. One real limitation of the existing data is the lack of a generally agreed upon and logistically feasible means of assessing iron status in free living humans. Further research, including basic research and large-scale epidemiologic studies, is needed to fully assess the association between iron status and the risk of CVD and other adverse outcomes. At present the currently available data do not support radical changes in dietary recommendations or screening to detect high normal levels nor do they support the need for large-scale randomized trials of dietary restriction or phlebotomy as a means of lowering iron stores.
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PMID:Iron status and risk of cardiovascular disease. 903 8

The oxidation of low density lipoprotein (LDL) within atherosclerotic lesions may be involved in atherogenesis. LDL oxidation by cells in the presence of iron is faster at acidic pH. In addition, LDL oxidation by iron alone or iron cysteine in the absence of cells is much faster at acidic pH, even at mildly acidic pH (pH 6.5). The effect of pH on LDL oxidation by copper ions is more complex, in that acidity slows down the initial oxidation, as measured by conjugated dienes, hydroperoxides and thiobarbituric acid-reactive substances, but can increase the later stages of LDL oxidation as measured by increased macrophage uptake. Extensive LDL oxidation by cells in atherosclerotic lesions probably requires a source of iron or copper as catalysts for the oxidation. Iron in plasma is carried by the protein transferrin. Lowering the pH releases some of the iron from transferrin so that it can catalyse LDL oxidation. Copper is carried in plasma on caeruloplasmin and becomes more effective in catalysing LDL oxidation when the caeruloplasmin is preincubated at acidic pH, or even at pH 7.0. These effects can be seen with concentrations of caeruloplasmin and transferrin below those present in plasma. By analogy to other inflammatory and ischaemic sites, atherosclerotic lesions may well have an acidic extracellular pH, particularly within clusters of macrophages where the oxidative stress may also be high. This localised acidic pH may help to explain why atherosclerotic lesions are one of the few sites in the body where extensive LDL oxidation occurs.
Atherosclerosis 1997 Mar 21
PMID:Does an acidic pH explain why low density lipoprotein is oxidised in atherosclerotic lesions? 910 56

It has been suggested that iron plays an important role in the pathogenesis of atherosclerosis, primarily by acting as a catalyst for the atherogenic modification of LDL. Although some epidemiological data suggest that high stored iron levels are an independent risk factor for coronary artery disease and that iron has been detected in both early and advanced atherosclerotic lesions, the evidence is often contradictory and inconclusive. We used the New Zealand White rabbit to investigate the effects of iron overload (FeO) and iron deficiency (FeD) on atherosclerosis. Groups of 7 rabbits were either iron loaded by injections of iron dextran (FeO group), iron depleted by phlebotomy (FeD group), or given injections of saline (control group) for a total of 9 weeks. All rabbits were fed a chow diet containing 1% (wt/wt) cholesterol for the last 6 weeks of the study. Iron and antioxidant status and cholesterol levels were assayed in plasma before cholesterol feeding (week 3) and at the time that the rabbits were killed (week 9). In addition, the susceptibility of LDL to oxidation was measured and pathological examination of the aortic arch and thoracic aorta performed at the end of the study. FeD significantly decreased the levels of blood hemoglobin, serum iron, and transferrin saturation compared with controls. Conversely, FeO significantly increased transferrin Fe saturation. FeO but not FeD decreased plasma cholesterol levels compared with control animals both before (P < .05) and after (P = .055) cholesterol feeding. Neither FeO nor FeD had a significant effect on the levels of antioxidants and lipid peroxidation products in plasma and aortic tissue or on the susceptibility of LDL to ex-vivo oxidation. FeO significantly decreased aortic arch lesion formation by 56% compared with controls (P < .05), whereas FeD had no significant effect. These results indicate that in this animal model, FeO decreases rather than increases atherosclerosis, likely because iron dextran exerts a hypocholesterolemic effect. Our data do not support the hypotheses that elevation of Fe stores increases or that a reduction of Fe stores by phlebotomy decreases the risk of coronary artery disease.
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PMID:Effect of iron overload and iron deficiency on atherosclerosis in the hypercholesterolemic rabbit. 940 37


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