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)

White Carneau (WC) pigeons are susceptible to the development of aortic atherosclerosis, whereas Show Racer (SR) pigeons are resistant, even though there are no differences in the known risk factors, including plasma cholesterol levels, lipoproteins, blood pressure, etc. Although this suggests that the difference in atherosclerosis susceptibility between WC and SR pigeons may be mediated at the level of the arterial wall, we have yet to identify a mechanism that can account for this difference. In pigeons as in other species (including humans), macrophages play a major role in the pathogenesis of atherosclerosis. Pigeon macrophages have multiple mechanisms for the uptake of lipoproteins and the accumulation of cholesteryl esters. To date, however, no differences in lipoprotein uptake between macrophages of WC and SR pigeons have been identified that could explain the difference in atherosclerosis susceptibility. In the present study we explored the alternative hypothesis that there are differences in the rate of cholesteryl ester clearance from peritoneal macrophages isolated from the two breeds of pigeons. Cholesterol efflux studies were conducted with elicited pigeon peritoneal macrophages that were loaded with cholesteryl ester either in vitro by incubation with rabbit beta-very low density lipoprotein or in vivo by isolation of macrophages from birds fed a cholesterol-containing diet. Using these techniques we were able to load WC and SR macrophages consistently with cholesteryl esters to levels typical of arterial foam cells (150-1,150 micrograms/mg cell protein). Under these cholesterol loading conditions there was no net efflux of cholesterol from either WC or SR macrophages when incubated for up to 24 hours in the presence of pigeon or human high density lipoprotein (HDL), fetal bovine serum, or lipoprotein-deficient serum. Under the same conditions, efflux of cholesterol from mouse peritoneal macrophages was stimulated by human and pigeon HDL. Despite the inability of HDL, lipoprotein-deficient serum, or fetal bovine serum to promote net cholesterol efflux, apoprotein (apo) HDL/phosphatidylcholine (PC) vesicles stimulated cholesteryl ester clearance from both WC and SR pigeon macrophages but at a significantly slower rate from WC pigeon macrophages. When incubated in the presence of excess apoHDL/PC (400 micrograms/ml), the rate of depletion of cellular cholesteryl esters was log-linear for at least 48 hours. WC macrophages cleared an average of only 9% of their cholesteryl esters in 24 hours when incubated with excess apoHDL/PC, whereas SR macrophages reduced their cholesteryl ester content by an average of 42%.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cholesterol efflux is defective in macrophages from atherosclerosis-susceptible White Carneau pigeons relative to resistant show racer pigeons. 142 89

In this study 126 subjects (91 males and 35 females, range of age 43-65 years) were studied by coronary angiography. We considered positive for coronary atherosclerosis also patients showing mild or moderate stenosis (> or = 25%). In all subjects we have evaluated serum lipid and apoprotein A-I, B, C-II, C-III and E levels; therefore also cholesterol concentrations in all lipoprotein fractions, separated by sequential ultracentrifugation (VLDL d < 1.006, LDL d 1.006-1.063, HDL d > 1.063 g/ml) and apoprotein B in LDL have been measured. Subjects with coronary atherosclerosis have shown significantly higher levels of total cholesterol, LDL-cholesterol, total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios than controls. Therefore, a lower apo A-I/apo B ratio in males and a higher LDL-apo B levels in females has been found in subjects with coronary atherosclerosis in comparison with controls. The stepwise multiple analysis has demonstrated that LDL-cholesterol levels is the parameter that best correlates with the presence of coronary atherosclerosis. These data confirm the importance of the reduction of LDL-cholesterol levels in primary and secondary prevention of coronary heart disease.
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PMID:[Lipids and serum apoproteins in subjects with slight or mild coronary atherosclerosis evaluated with angiography]. 142 68

apoE-deficient mice have been created by homologous recombination in ES cells. On a low fat, low cholesterol chow diet these animals have plasma cholesterol levels of 494 mg/dl compared with 60 mg/dl in control animals, and when challenged with a high fat Western-type diet, these animals have plasma cholesterol levels of 1821 mg/dl compared with 132 mg/dl in controls. This marked hypercholesterolemia is primarily due to elevated levels of very low and intermediate density lipoproteins. At 10 weeks of age, apoE-deficient mice have already developed atherosclerotic lesions in the aorta and coronary and pulmonary arteries. apoE-deficient mice are a promising small animal model to help understand the role of apoE in vivo and the genetic and environmental determinants of atherosclerosis.
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PMID:Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. 142 98

Plasma lipids and apoprotein A and B levels were measured in 63 children, of both sexes, in the age range 11-14 years. The children have been subjected to a blood drawing after a 12 hour fast at least. Statistical analysis proves that total cholesterol (TC) is positively correlated with triglycerides (TG), HDL cholesterol (HDL) with apolipoproteins A (Apo A), apolipoproteins A (Apo A) with apoproteins B (Apo B). In the end we confirm the utility of determining plasma lipids and apoproteins to estimate lipidic risk for atherosclerosis in pediatric age.
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PMID:[Plasma levels of lipids and apoprotein in a group of middle-school students 11-14 years of age: preliminary data]. 146 2

Total serum IgA and IgA antibodies to some milk antigens are often associated with severe atherosclerosis. In the present study we examined the same serum samples to evaluate the possible involvement of serum IgA antibodies to apoproteins and lipoproteins and their relationship to IgA antibodies to milk antigens. We studied 23 subjects with angiographically assessed atherosclerotic lesions (ATS group) and 20 healthy control subjects with a similar age range (59-69 years) and sex distribution. Anti-ApoB, Apo A-I, Apo A-II and anti-LDL, VLDL and HDL antibodies were measured with the ELISA method. All antibodies tested except those to anti-Apo A-I were significantly higher in the ATS group with respect to controls with a maximum significance for anti-Apo B IgA (p = 0.0018). When, for each antibody, a threshold of positivity was set to the mean + 2 SD of values in the control group, 12 ATS subjects (52%) and 1 control (5%) were found to be positive for either anti-Apo B or anti-Apo A-II IgA. Most of the correlations of anti-apoprotein and anti-lipoprotein IgA with anti-milk protein IgA and total IgA were significant. The association of these antibodies with atherosclerosis might either be specific or represent part of a polyclonal IgA response. Whether this association is a cause or an effect of atherosclerotic disease is presently unknown.
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PMID:Serum IgA antibodies to apoproteins and milk-proteins in severe atherosclerosis. 152 49

Because the accumulation of lipid in macrophages is a characteristic feature of atherosclerosis, the mechanisms by which this lipid accumulation occurs have been intensively studied. This paper reviews the receptor- and non-receptor-mediated pathways that promote lipid accumulation in macrophages. Particular emphasis is placed on the contributions of two secretory products of macrophages, lipoprotein lipase and apolipoprotein E, to both receptor- and non-receptor-mediated uptake of triglyceride-rich lipoproteins by macrophages. The hormonal, lipid, and immunological factors that regulate the secretion of LpL and apoE by macrophages are discussed, as are how changes in the secretion of apoE and LpL that can modulate the uptake of triglyceride-rich lipoproteins by macrophages might influence the atherosclerotic process in people with diabetes.
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PMID:Role of lipoprotein lipase and apolipoprotein E secretion by macrophages in modulating lipoprotein uptake. Possible role in acceleration of atherosclerosis in diabetes. 152 41

Increased plasma levels of the apoB-100-containing lipoprotein(a) (Lp(a)) are associated with an increased risk for atherosclerosis and myocardial infarction, but the mechanisms by which lipoprotein(a) may accelerate these processes remain obscure. In this study we have investigated the impact of the association of apoprotein(a) with the low density lipoprotein (LDL)-like Lp(a) particle upon specificity of receptor recognition after lipoprotein modification by malondialdehyde or transition metal-induced oxidation. We have determined that radioiodination labels both apoprotein components of Lp(a), that malondialdehyde modification produces an anionic lipoprotein comparable to native Lp(a) in Stokes' radius, and that N,N'-disubstituted 1-amino-3-iminopropene derivatives preferentially cross-link apoprotein(a) to apoB-100 protein. Like LDL, native Lp(a) is recognized in human monocyte-macrophages by the LDL receptor. Like LDL, progressive modification of Lp(a) by malondialdehyde abolishes lipoprotein recognition by the LDL receptor and produces uptake and hydrolysis by the scavenger receptor of human monocyte-macrophages. We propose that intimal retention of Lp(a) by extracellular components of the atherosclerotic reaction places the lipoprotein in a microenvironment favoring subsequent peroxidative modification. The chronic production of lipid peroxide-modified Lp(a) together with unmitigated cellular clearance by scavenger receptors may contribute to the accumulation of lipoprotein-derived lipid in macrophage-derived foam cells of the atherosclerotic reaction.
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PMID:Malondialdehyde modification of lipoprotein(a) produces avid uptake by human monocyte-macrophages. 153 81

Lipoprotein(a) (Lp[a]), a highly atherogenic lipoprotein particle, is the prominent apolipoprotein B-containing lipoprotein in the hedgehog (Laplaud PM et al, J Lipid Res 1988;29:1157-1170). In the present work, we studied the consequences of the structural homology between the specific Lp(a) glycoprotein, apoprotein(a), and plasminogen on the generation of plasmin by fibrin-bound tissue-type plasminogen activator. The activation of plasminogen was initiated by adding either native plasma or Lp(a)-free plasma supplemented with the equivalent of 0.25 mg/ml of either purified Lp(a) or albumin to a surface of fibrin prepared on micortitration plates and to which human tissue-type plasminogen activator was specifically bound. With the Lp(a)-free plasma, an increase in the binding and activation of plasminogen as a function of time was observed. In contrast, in the presence of Lp(a) (i.e., native plasma or the reconstituted system), a significant decrease in the binding of plasmin(ogen) (approximately 60%) was obtained. These data indicate that hedgehog Lp(a) interferes with the binding and activation of plasminogen at the fibrin surface and may thereby behave as a factor regulating the extent of fibrin deposition. These results support our previous data indicating that high levels of Lp(a) may have antifibrinolytic effects in humans (Rouy D et al, Arterioscler Thromb 1991;11:629-638), are in agreement with the observation that Lp(a) is a risk factor for atherosclerotic disease, and provide further support to the view of Lp(a) as a link between atherosclerosis and thrombosis.
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PMID:Hedgehog lipoprotein(a) is a modulator of activation of plasminogen at the fibrin surface. An in vitro study. 153 29

The oxidative modification of low-density lipoprotein (LDL) is suggested to play an important role in the pathogenesis of atherosclerosis. The present study examined the role of the formation of LDL-copper (Cu) complex in the peroxidation of LDL. The amount of copper bound to LDL increased during incubation performed with increasing concentrations of CuSO4. More than 80% of the copper bound to the LDL particle was observed in the protein phase of LDL, suggesting that most of the copper ions formed complexes with the ligand-binding sites of apoprotein. The addition of histidine (1 mM), known to form a high affinity complex with copper, and EDTA (1 mM), a metal chelator, during the incubation of LDL with CuSO4 prevented the formation of both thiobarbituric acid-reactive substances (TBARS) and LDL-Cu complexes. EDTA inhibited the copper-catalyzed ascorbate oxidation whereas histidine had no effect, suggesting that the copper within the complex with histidine is available to catalyze the reaction, in contrast to EDTA. These observations indicate that the preventive effect of histidine on the copper-catalyzed peroxidation of LDL is not simply mediated by chelating free copper ions in aqueous phase. Evidence that copper bound to LDL particle still has a redox potential was provided by the observed increase in TBARS content during incubation of LDL-Cu complexes in the absence of free copper ions. The addition of either histidine or EDTA to LDL-Cu complexes inhibited the formation of TBARS by removing copper ions from the LDL forming the corresponding complexes. However, there still remained small amounts of copper in the LDL particles following the treatment of LDL-Cu complexes with histidine or EDTA. The copper ions remaining in the LDL particle lacked the ability to catalyze LDL peroxidation, suggesting that there may be two types of copper binding sites in LDL: tight-binding sites, from which the copper ions are not removed by chelation, and weak-binding sites, from which copper ions are easily removed by chelators. The formation of TBARS in the LDL preparation during incubation with CuSO4 was comparable to the incubation with FeSO4. In contrast, the formation of TBARS in the LDL-lipid micelles by CuSO4 was nearly eliminated even in the presence of ascorbate to promote metal-catalyzed lipid peroxidation, although a marked increase in TBARS content was observed in the LDL-lipid micelles with FeSO4, and with FeCl3 in the presence of ascorbate.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of lipoprotein-copper complex in copper catalyzed-peroxidation of low-density lipoprotein. 153 73

Previous results, presented in abstract form, indicate that replacement of thromboplastin with a mixture of phospholipid and truncated soluble tissue factor apoprotein results in a coagulation assay that can directly measure plasma factor VIIa levels without interference from zymogen factor VII (Atherosclerosis Thromb 11:1544a, 1991 [abstr]). We have exploited the specificity and sensitivity of such a factor VIIa specific coagulation assay to directly assess the in vivo relationship of factor VIII and factor IX on the production of factor VIIa levels under nonthrombotic and nonstimulatory conditions. Normal individuals (n = 20) were found to possess an average circulating factor VIIa level corresponding to 4.34 +/- 1.57 ng/mL, or approximately 1% of their total factor VII antigen. Severe factor VIII deficient patients (n = 13) possessed a slightly lower but statistically significant (P less than .01) decrease in their basal factor VIIa levels (2.69 +/- 1.52 ng/mL), corresponding to approximately 60% of that observed in normal individuals. On the other hand, severe factor IX deficient patients (n = 7) were found to possess even lower levels of factor VIIa corresponding to 0.33 +/- 0.15 ng/mL, or less than 10% of that observed in normal individuals. Measurement of total factor VII antigen levels shows that the variation in basal factor VIIa levels stems from differences in the degree of factor VII activation as opposed to differences in factor VII antigen levels. Our present data are consistent with the hypothesis that factor IXa is the principal in vivo activator of factor VII under basal conditions.
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PMID:Measurement of basal levels of factor VIIa in hemophilia A and B patients. 146 30

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