UMLS:C0004153 - FACTA Search

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

Accumulative evidence has supported the role of iron in the development of atherosclerosis. To test whether iron-mediated oxidative stress influences plaque stability, apoliporotein-E (ApoE)-deficient mice (3 months old) were placed on a chow diet or a low-iron diet for 3 months, and the abundance of interstitial collagen and the expression of the matrix degradation-associated enzyme, matrix metalloproteinase-9 (MMP-9), in vascular lesions were assessed. A low-iron diet appeared to reduce iron deposition while substantially increasing collagen content of lesions in mice. Immunostaining demonstrated lower expression of MMP-9 in lesions of iron-restricted animals. Likewise, SDS-PAGE zymography revealed lower gelatinolytic activities in aortic tissues and sera of the same group of animals. When older ApoE-deficient mice (5 months old) received a low-iron diet for 2 months, development of the lesion area was not significantly affected. However, the lesional collagen content was much higher in the iron-restricted group of animals, and MMP-9 expression in aortic tissues from the same group of mice was significantly lower. Treatment of murine J774 macrophages with increasing concentrations of ferric ammonium citrate significantly enhanced the amount of MMP-9 secreted. Together, these data indicate that decreased vascular iron content following dietary iron restriction in ApoE-deficient mice leads to lower matrix degradation capacity and increased plaque stability.
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PMID:Dietary iron restriction increases plaque stability in apolipoprotein-e-deficient mice. 1292 91

Scintigraphic imaging of radiolabeled low-density lipoproteins (LDL) is an interesting tool for the understanding of its role in pathomechanism of atherosclerosis. Metabolism of native LDL shows quite different pattern and kinetics as compared to that of modified LDL which is not mediated by classical LDL-receptor and accumulates in atherosclerotic lesions to form lipid-laden foam cells. Therefore we were interested whether radiolabelling of LDL induces structural modifications. We performed the iodine labeling of LDL for scintigraphic imaging of atherosclerosis by three different methods: chloramine-T (A), iodine monochloride (B) and iodogen (C). The highest radiolabelling yield of (125)I was obtained by the iodogen method (75.44+/-13.52%) and the lowest (49.01+/-12.74%) by iodine monochloride. Chloramine T showed a labeling yield of 62.82+/-6.17%. The stability of the tracer was very high with all the methods, persisting up to 6 h (98.83+/-1.2% - 91.38+/-4.7%, 15 min vs 6 h after labeling). For the first time we not only investigated the influence of radiolabelling on relative electrophoretic mobility (REM), but also various oxidation parameters such as baseline dienes (BD), thiobarbituric acid reactive substances (TBARS), endogenous peroxides (POX) and oxidation resistance in the copper-mediated oxidation system (expressed as lag-time) were measured. Furthermore, oxidation- derived fragmentation of the lipoproteins was examined with SDS-PAGE electrophoresis. Data are expressed as % change compared to native LDL before radiolabeling. BD were reduced by 32% using the method (A), but increased by 33% and 47% with the monochloride (B) and iodogen method (C), respectively. The effect on lag-time was comparable for all the three methods, ranging from 25 to 36% reduction in lag-time. TBARS were strongly increased 5-7 fold by all the methods. REM was changed by all three methods. While by methods A and C we have found a moderate increase in REM by 1.75 and 2.0 fold, respectively, and no fragmentation of Apo B was observed, in contrast by method B a dramatic 4.5 fold increase in REM was found. SDS-PAGE-electrophoresis showed strong fragmentation of the apoB only for method B. We conclude, that iodine labeling of LDL induces significant modification of the molecule. Once modified, LDL no longer reflects the native molecule, exhibiting altered functional properties. Using radiolabeled LDL this fact should be considered.
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PMID:Modification of low-density lipoprotein by different radioiodination methods. 1502 51

Reactive oxygen species (ROS) are associated with aging and the correlation between Alzheimer's disease and atherosclerosis is a subject of the discussion. The aim of this study was to determine whether genetic factors affect cellular defense against cytotoxic beta-amyloid (Abeta) which is considered to be the source of ROS. Low levels of Abeta (1-10 microM) led to a significant suppression of redox potential as measured by MTT assay in bone marrow-derived cell lines. The atherosclerosis-resistant cells (GG2EE) were less affected than the susceptible cells (ANA1) in the time-, dose-, and Abeta species-dependent manner. Cell death in amyloid treated resident susceptible macrophages (C57BL/6J), measured by lactate dehydrogenase release, was induced during prolonged incubation and increased when compared with the resistant macrophages (C3H/HeJ, P = 0.005). SDS-PAGE showed that Abeta persisted intracellularly during this period. The cytotoxicity of oxidized low density lipoproteins (oxLDLs) significantly affected only the susceptible cells which actually lowered this cytotoxicity, thus, implying that the harmful effect of the oxLDLs was diminished when compared to that of Abeta. This fact demonstrates that in vitro the defense by cells of monocyte origin against Abeta may be determined in part genetically whereas the reaction to oxLDLs could be fully underlined by genetic susceptibility.
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PMID:Cellular defense against oxidized low density lipoproteins and fibrillar amyloid beta in murine cells of monocyte origin with possible susceptibility to the oxidative stress induction. 1503 16

Raised levels of chylomicrons and chylomicron remnants, which circulate following a meal, have been implicated in the development of atherosclerosis. Apolipoprotein (apo) B-48 is exclusively associated with chylomicron particles and provides a specific direct measurement of the number of intestinally derived lipoproteins in the circulation. The quantification of apo B-48 in biological samples is difficult due to the very low concentration in plasma, structural similarity to the N-terminal 48% of apo B-100 and lack of an appropriate standard for apo B-48. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), followed by coomassie blue staining, has been used for many years to measure apo B-48 levels in triacylglycerol (TAG)-rich lipoprotein samples. The raising of antiserum to apo B-48 has led to development of more sensitive and specific methods including immunoblotting and enzyme-linked immunosorbant assays (ELISAs). This has enabled direct measurement of apo B-48 in plasma without the need for separation into TAG-rich lipoproteins. A high degree of variability was observed in the apo B-48 concentrations reported in the literature both within and between the SDS-PAGE, immunoblotting and ELISA methods.
Atherosclerosis 2004 Oct
PMID:Apolipoprotein B-48: comparison of fasting concentrations measured in normolipidaemic individuals using SDS-PAGE, immunoblotting and ELISA. 1538 Apr 42

Vascular smooth muscle cell (VSMC) proliferation and proteoglycan biosynthesis are two critical contributors to the development of atherosclerosis. We investigated the effects of specific androgens, androstenedione, dihydrotestosterone, and testosterone, on proteoglycan biosynthesis in human VSMC derived from internal mammary arteries. Vascular SMCs were metabolically labeled with [(35)S]sulfate or [(35)S]methionine/cysteine to assess glycosaminoglycans (GAGs) or proteoglycan core protein, respectively. The electrophoretic migration of radiolabeled proteoglycans was assessed by SDS-PAGE. Proteoglycan-low density lipoprotein (LDL) interactions were assessed using LDL affinity columns. Treatment of VSMCs with androstenedione (100 nm), dihydrotestosterone (10 nm), or testosterone (100 nm) increased [(35)S]sulfate incorporation into GAGs by 24.8% (P < 0.05), 22% (P < 0.05), and 32.5% (P < 0.05), respectively. Treatment of VSMCs with testosterone did not alter [(35)S]methionine/cysteine incorporation into proteoglycan core protein, suggesting that the effect of testosterone was associated with an increase in GAG length. Dihydrotestosterone (10 nm) and testosterone (100 nm) treatment of VSMCs resulted in the synthesis of biglycan and decorin that showed reduced electrophoretic mobility by SDS-PAGE, indicating an increase in GAG length. The effect of testosterone treatment on [(35)S]sulfate incorporation and GAG length was reversed by pretreatment of VSMCs with flutamide (1 mum), an androgen receptor antagonist. Proteoglycans from VSMCs treated with testosterone showed 11% (P < 0.01) higher binding capacity to LDL compared with proteoglycans from untreated cells. These results suggest a possible proatherogenic action of androgens through an elongation of GAG chains on proteoglycans in an androgen receptor-dependent manner.
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PMID:Androgens stimulate human vascular smooth muscle cell proteoglycan biosynthesis and increase lipoprotein binding. 1566 61

The accumulation of extracellular matrix components such as proteoglycans is a hallmark of an atherosclerotic lesion. A large heparan sulfate proteoglycan, perlecan, dramatically increases in the advanced lesion, and vascular smooth muscle cells are the cell type responsible for the accumulation. In this study, we investigated the effects of thrombin on the proteoglycan synthesis in cultured human coronary smooth muscle cells to determine the interrelationship between the accumulation of proteoglycans and the procoagulant state of blood in atherosclerosis. The cells were metabolically labeled with [(35)S]sulfate or (35)S-labeled amino acids in the presence of thrombin, and the labeled proteoglycans were characterized by Sepharose CL-4B molecular sieve chromatography and DEAE-Sephacel ion-exchange chromatography. The glycosaminoglycan M(r) and composition were analyzed by Sepharose CL-6B chromatography, and the core protein M(r) was determined by SDS-polyacrylamide gel electrophoresis before and after digestion with chondroitinase ABC or papain. The results indicate that thrombin increases the cell layer-associated heparan sulfate proteoglycan with a core protein size of approximately 400 kDa without any change in the length of the glycosaminoglycan chains when the cell density is high. The heparan sulfate proteoglycan was identified as perlecan by Western blot analysis. In addition, quantitative reverse transcription-polymerase chain reaction showed that thrombin elevated the steady-state level of perlecan mRNA but not that of versican, decorin, and syndecan-1 mRNAs, although that of biglycan mRNA was moderately elevated. Furthermore, the percentage of disaccharide units that compose perlecan heparan sulfate chains remained unaffected by thrombin. Therefore, it is suggested that thrombin induces the perlecan core protein synthesis without influencing the formation of the heparan sulfate chains in human coronary smooth muscle cells at a high cell density. The regulation of proteoglycan synthesis by thrombin may be involved in the accumulation of perlecan in advanced lesions of atherosclerosis.
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PMID:Induction of synthesis of a large heparan sulfate proteoglycan, perlecan, by thrombin in cultured human coronary smooth muscle cells. 1571 25

Previous studies have demonstrated endogenous formaldehyde (FA) may be involved in endothelial damage, and may be a potential factor of vulnerability of atherosclerosis. However, the mechanism has not been characterized. The present studies examined DNA-protein cross-links (DPC) formation in rat aorta endothelial cells (RAECs) treated with formaldehyde, hydrogen peroxide (H2O2), or formaldehyde with equal molar concentration of H2O2, which is produced with formaldehyde in the body at the same time. Using a K+/SDS precipitation assay for DPC determination, concentration-dependent increases in DPC formation were observed 1.5 h after treatment of RAECs with 0.01-2mM FA, H2O2, or FA with equal molar concentration of H2O2. Time-dependent increases in DPC formation were also observed at 0.5-4 h time point after treatment of RAECs with 0.05 and 0.1mM FA, or 0.1mM FA with H2O2. The DPC levels reduced after treatment with FA and equal molar concentration of H2O2, compared with treatment with FA alone. FA may be less cytotoxic, as FA alone did not affect the cell viability even treating for 4h, until the treatment concentration reached 2mM. However, H2O2, and FA with H2O2 induced significant decreases of cell viability. These studies suggest that FA and H2O2 may injure endothelial cells synergistically, and low concentration of FA (0.05-0.1) may contribute to the endothelial injury in the body during aging.
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PMID:The effect of endogenous formaldehyde on the rat aorta endothelial cells. 1596 Dec 63

Sphingomyelin (SM) plays a very important role in cell membrane formation and plasma lipoprotein metabolism. All these functions may have an impact on atherosclerotic development. To investigate the relationship between SM metabolism and atherosclerosis, we utilized a sphingolipid-rich diet to feed LDL receptor gene knockout (LDLr KO) mice and studied lipid metabolism and atherosclerosis in the mice. After 3 months of a sphingolipid-rich diet, we found a significant increase in SM, cholesterol, and SM/phosphatidylcholine (PC) ratio (50%, P<0.001; 62%, P<0.01; and 45%, P<0.01, respectively), compared to chow fed diet. HDL-lipids were not significantly altered. Non-HDL-SM, non-HDL-C, and non-HDL-SM/non-HDL-PC ratio were significantly increased (115%, P<0.001; 106%, P<0.001; and 106%, P<0.01, respectively). FPLC confirmed the results. SDS-PAGE showed an increase of apoB48 and apoB100, but no changes of apoAI. Moreover, we found that an SM-rich diet significantly increased atherosclerotic lesion area in both root assay and en face assay, compared to chow diet (58,210+/-15,300 microm(2) vs. 9670+/-2370 microm(2), P<0.001; 5.9+/-3.1% vs. 1.1+/-0.9%, P<0.001). These results indicate that the enrichment of sphingolipids in diet has proatherogenic properties.
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PMID:The effect of dietary sphingolipids on plasma sphingomyelin metabolism and atherosclerosis. 1596 15

Enolase, is a glycolytic enzyme ubiquitous in higher organisms, where it forms tissue specific dimers of isoforms, also found in the cytoplasm of fermentative bacteria. The aim of this work was to identify enolase-like proteins in the cell wall of some Gram-negative bacteria using antibodies against human beta-enolase, an isoenzyme specific to skeletal and heart muscles. Cell wall outer membrane protein (OMP) preparations were obtained from 9 strains of Enterobacteriaceae and one of Pseudomonas aeruginosa. Specific enzymatic enolase activity was detected in the supernatant fractions of cytosolic and inner membrane material, but not in purified OMP preparations. Rabbit polyclonal antibodies specific against human beta-enolase were prepared and purified using immobilized human beta-enolase in affinity chromatography. In SDS-polyacrylamide gel electrophoresis and immunoblotting assay of purified OMP preparations, rabbit anti-enolase antibody interacted specifically with a few OMPs, of which a 45-kDa band also interacted with human sera of patients presenting Buerger disease and atherosclerosis. The most distinct interaction of human sera was observed with a 45-kDa OMP of Klebsiella pneumoniae. This protein was further isolated from K. pneumoniae cell mass in two ways, namely preparative SDS-polyacrylamide gel electrophoresis and specific affinity chromatography using immobilized affinity-purified rabbit antibody raised against human beta-enolase. The data obtained from tandem mass spectrometry tryptic peptide analysis and sequence comparison of human and bacterial enolases using protein databases, could reveal the similarity in the epitopes between membrane enolase-like protein from Klebsiella and human beta-enolase. The results show that the protein present in all studied strains has a common epitope on human beta-enolase. These data raise the question whether such a bacterial protein might be a marker for detecting and monitoring damage to skeletal and heart muscles.
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PMID:Antibodies against human muscle enolase recognize a 45-kDa bacterial cell wall outer membrane enolase-like protein. 1598 23

The aim of this study was to evaluate the antioxidant activity of HDL with aging and to investigate the implication of PON1 in this process. The study involved 54 healthy subjects distributed in two age groups, young (20-25 years) and elderly (65-85 years). Lipid peroxidation was induced by *OH and O2*- oxygen free radicals produced by gamma-radiolysis of water. LDL oxidation was followed by the measurement of conjugated diene (CD), lipid peroxide (LP) and malondialdehyde (MDA) formation. PON1 was purified separately from young (Y-PON1) and elderly subjects (E-PON1). PON1 activity and structure was followed by measurement of PON1 paraoxonase (p.ase) activity, titration of the SH groups, and electrophoretic mobility by SDS-PAGE. Our results show a significant decrease in the HDL antioxidant activity: percentage of protection against CD formation=27.70% (p<0.01) for E-HDL versus 73.08% (p<0.001) for Y-HDL. Moreover, E-PON1 showed a lower antioxidant activity when compared to Y-PON1 47.08% versus 78.14%, respectively (p<0.0001). Exposition of PON1 to *OH and O2*- oxygen free radicals induced a significant decrease in PON1 p.ase activity as well as a reduction in the number of PON1's free sulfhydryl groups. Moreover, our results show a close association between PON1's free sulfhydryl groups and its capacity to protect LDL against lipid peroxidation. There was a significant decrease in the number of free sulfhydryls between Y-PON1 and E-PON1 with respect to cysteine-284 amino acid residues (p<0.0092).
Atherosclerosis 2006 Mar
PMID:Age-related decrease in high-density lipoproteins antioxidant activity is due to an alteration in the PON1's free sulfhydryl groups. 1602 89

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