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)

Thirty hyperlipidaemic patients (19 with type IIA, 4 with IIB and 7 with type IV hyperlipoproteinaemia) were subjected to therapy with calcium clofibrate and calcium carbonate (4C, 2 + 2 g/day for 6 months) and the effect was compared with clofibrate (1C, 2 g/day) which was given for 6 months as well, in a single-blind placebo-controlled study. 4C and 1C decreased total serum cholesterol levels especially in subgroups IIA and IIB. 4C was somewhat more effective than 1C in decreasing (VLDL + LDL)-cholesterol in subgroup IIA. The HDL-cholesterol concentrations and the ratio of HDL-cholesterol and total cholesterol increased during treatment with both 1C and 4C. The HDL-cholesterol increase (vs. placebo) was 18%. The concentrations of serum triglycerides decreased by 33% during both treatment periods and there was no significant difference between 1C and 4C.
Atherosclerosis 1979 May
PMID:Long-term effect of the combination of calcium clofibrate and calcium carbonate on serum total cholesterol, triglyceride and high density lipoprotein--cholesterol concentrations in hyperlipoproteinaemia. A comparative study with clofibrate. 22 1

Development of the mineralization process in the course of atherogenesis was studied using the cholesterol-fed rabbit model. The aorta samples were investigated by means of proton and electron microprobes, infrared spectroscopy and X-ray diffraction as well as selected histochemical staining. Blood serum was analysed every 2 weeks to determine the content of cholesterol, triglycerides, inorganic phosphorus, ionized calcium, elemental composition as well as activity of alkaline phosphatase. It was found that the administered diet did not disturb the calcium and phosphorus homeostasis. Histochemical findings confirmed the formation of lipid-rich lesions blocking the lumen of the vessel. The dystrophic calcification was observed only in the atheroma, while in the tunica media a slight mineralization similar to that found in controls was observed after 210 days of the diet. In the atheroma the only phase detected was a defective hydroxyapatite. The perfection of the crystals, as well as the diameter of the deposits, increased during the course of the diet reaching about 2 microns after 210 days. The crystals were not contaminated with carbonate groups regardless of the duration of the diet.
Atherosclerosis 1991 Apr
PMID:Calcification of aortic wall in cholesterol-fed rabbits. 185 64

Calcified human aortic atherosclerotic deposits and calf ventricular assist device bioprosthetic deposits were isolated and deproteinated by hydrazine treatment. Detailed chemical and instrumental analyses were applied to gain comprehensive physicochemical information which makes possible establishing compositional and structural similarities between the 2 types of pathologic mineral deposits which form on different host surfaces. These microcrystalline deposit materials are morphologically very heterogeneous and can be represented chemically as carbonate substituted apatite which, in some of its properties, significantly differs from hydroxyapatite. It is indicated that the mechanism for the formation of cardiovascular deposits proceeds through hydrolysis of octacalcium phosphate precursor.
Atherosclerosis 1988 Jan
PMID:Physiochemical characterization of cardiovascular calcified deposits. I. Isolation, purification and instrumental analysis. 328 78

Neutral, uncharged binding sites for calcium ions are proposed for elastin and collagen. The sites utilize, particularly from a conformational viewpoint, the most striking feature of the amino acid composition, that is, the high glycine content. Glycines favor the formation of beta-turns and associated conformations that are known, from studies on ion-transporting antibiotics, to interact with cations. By analogy with certain antibiotics, which are uncharged polypeptides and depsipeptides that bind cations by coordination with neutral acyl oxygens, it is proposed that calcium-ion binding also utilizes uncharged coordinating groups, i.e., neutral sites, in the protein matrix. The protein matrix, which becomes positively charged by virtue of the bound calcium ions, attracts neutralizing phosphate and carbonate ions, which then allow further calcium ion binding. The driving force is, therefore, the affinity of calcium ions for the neutral nucleation sites. The charge neutralization theory of calcification suggests a fundamental role of organic anions, for example sulfated mucopolysaccharides, in regulating bone formation and in retardation of atherosclerosis. The proposed mechanism contains elements that tend to unify several theories on the pathogenesis of atherosclerosis.
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PMID:Neutral sites for calcium ion binding to elastin and collagen: a charge neutralization theory for calcification and its relationship to atherosclerosis. 425 54

The results of morphological studies on the structure of mineral deposits in the walls of major arteries in atherosclerosis are presented. Calcium deposits looking like petrificates and microgranular deposits were found. The petrificates consisted of microgranular, microcrystalline and macrocrystalline deposits of calcium salts. In the arterial wall, the crystals consisted of calcium phosphate and calcium carbonate. The relationship between the destruction of elastic fibers and elastic membranes and calcification of the vascular wall was confirmed.
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PMID:[Structure of the mineral deposits in major arterial walls in calcinosis (based on scanning electron microscopic data)]. 663 99

The mineral deposits of the human atherosclerotic aorta were prepared by a new method characterized by the use of mild conditions. Both large and small mineral deposits were isolated from the atherosclerotic plaque and were shown to possess essentially the same chemical composition. The deposits consisted mainly of calcium apatite (71%), carbonate (9%) and contained a relatively high percentage of protein (15%). X-ray diffraction pattern analysis revealed the presence of microcrystals with an average size of approximately 0.1 micron. Electron probe analysis showed that the surface and interior of the mineral deposit had the same chemical composition. However, scanning electron microscopy revealed that the deposits were heterogeneous and consisted of five different structures: (1) individual and conglomerates of smooth-surfaced apheres consisting of spherical layers; (2) spheres consisting of spindle-like, radially arranged particles; (3) fibres forming networks and bundles which sometimes included spherical particles; (4) irregularly shaped particles with fuzzy surfaces and (5) flat plates with smooth surfaces.
Atherosclerosis 1980 Oct
PMID:Chemical and physicochemical studies on the mineral deposits of the human atherosclerotic aorta. 742 95

To determine whether metastatic calcification during neointima formation can result in neointimal calcification that simulates advanced human atherosclerosis, 32 giant Flemish rabbits (weight 5.5 +/- 0.6 kg) underwent overstretch balloon injury of bilateral iliac arteries and received diet therapy for 8 weeks: high cholesterol (2%) and low calcium-vitamin D2 regimen (250 mg of calcium carbonate orally 5 times weekly and 50,000 U of calciferol intramuscularly 3 times weekly; group 1; n = 5); low cholesterol (0.5%) and high calcium-vitamin D2 regimen (500 mg of calcium carbonate orally 5 times weekly and 100,000 U of calciferol intramuscularly three times weekly; group 2; n = 19); or 0% cholesterol and high calcium-vitamin D2 regimen (group 3; n = 8). The incidence of vascular calcification was highest (71.4%) in group 2. Eighty-one percent of calcification was medial. Residual strain measurements of 7 thoracic aortas from group 2 compared to normal thoracic aortas from 8 control rabbits showed that residual strain was significantly increased in the calcified atherosclerotic aortas (12.3% vs 5.2%; p = 0.001). We conclude that diet-induced hypercalcemia predominantly affects the media despite the presence of concomitant neointima formation from balloon artery injury with or without hypercholesterolemia and increases the residual strain more than twofold compared to normal thoracic aortas.
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PMID:Vascular effects of diet-induced hypercalcemia after balloon artery injury in giant Flemish rabbits. 757 83

Nitric oxide reacts with superoxide to form peroxynitrite, a potential mediator of oxidant-induced cellular injury. The endothelium is a primary target of injury in many pathological states, including acute lung injury, sepsis, multiple organ failure syndrome, and atherosclerosis, where enhanced production of nitric oxide and superoxide occurs simultaneously. It was hypothesized that stimulation of endothelial cell nitric oxide production would result in formation of peroxynitrite. Immediate oxidant production was detected by luminol- and lucigenin-enhanced chemiluminescence from cultured bovine aortic endothelial cells exposed to bradykinin or to the calcium ionophore A23187. Luminol-enhanced chemiluminescence was efficiently inhibited by the nitric oxide synthase inhibitor nitro-L-arginine methyl ester and by superoxide dismutase, implying dependence on the presence of both nitric oxide and superoxide for oxidant production. Inhibition of luminol-enhanced chemiluminescence by nitro-L-arginine methyl ester was partially reversed by L-arginine, but not by D-arginine. Cysteine, methionine, and urate, known inhibitors of peroxynitrite-mediated oxidation, inhibited luminol-enhanced chemiluminescence, while the hydroxyl radical scavengers, mannitol and dimethylsulfoxide, and catalase did not. Bicarbonate increased luminol-enhanced chemiluminescence in a concentration-dependent manner. Superoxide production, detected by lucigenin-enhanced chemiluminescence, was slightly increased in the presence of nitro-L-arginine methyl ester, suggesting that endothelial cell-produced superoxide was partially metabolized by reaction with nitric oxide. These results are consistent with agonist-induced peroxynitrite production by endothelial cells and suggests that peroxynitrite may have an important role in oxidant-induced endothelial injury.
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PMID:Agonist-induced peroxynitrite production from endothelial cells. 817 19

Lipid hydroperoxides have been implicated in the pathogenesis of atherosclerosis. This work was therefore set up to obtain a fast and specific chemiluminescent assay for measuring hydroperoxides in native low-density lipoprotein (LDL). The apparatus was a complete HPLC system including two pumps, an autosampler, a computer and a chemiluminescent detector with a T-mixing coil in the place of the column. Samples were injected from the autosampler and mixed with luminescent reagent (3 microM luminol and 1 microM microperoxidase in 0.1 M carbonate buffer (pH 10)) in the T-piece. To generate a calibration curve, linoleic acid hydroperoxide was obtained by incubating soybean lipoxygenase with linoleic acid. The calculated conjugated diene concentration was in good agreement with the nominal linoleic acid hydroperoxide concentration. The chemiluminescence was linear with the amount of linoleic acid hydroperoxide injected and the detection limit was about 3 pmol linoleic acid hydroperoxide. The chemiluminescence induced by copper-oxidized LDL was linear with concentration; the detection limit, when compared with linoleic acid hydroperoxide, was similar. The reproducibility of the linoleic acid hydroperoxide and of oxidized LDL hydroperoxide was examined in single pools. The coefficient of variation on the triplicates of each pool was about 3%. The titre of the linoleic acid hydroperoxide and oxidized LDL peroxides was quite stable for at least 10 days when stored under argon at 4 degrees C in the presence of EDTA. The mean value of the LDL hydroperoxides in 16 control subjects was 145.20 +/- 98.81 pmol/mg LDL protein. In conclusion, the microperoxidase-luminol-dependent chemiluminescence flow-injection assay is a rapid, sensitive and selective method for measuring lipid hydroperoxides in native LDL.
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PMID:Determination of lipid hydroperoxides in native low-density lipoprotein by a chemiluminescent flow-injection assay. 841 85

After investigation of the contents and redox status of antioxidants and lipids in homogenates of both normal artery and atherosclerotic plaque, we now investigated them in the density fractions (very low, low, high, and protein fractions) of atherosclerotic plaque freshly obtained from carotid endarterectomy. By using the optimum extraction method (homogenization in carbonate buffer) and after density gradient ultracentrifugation, we isolated and characterized density fractions of plaque for apolipoproteins, size and contents of alpha-tocopherol (alpha-TOH), unesterified cholesterol, cholesteryl linoleate (Ch18:2), and hydroxides and hydroperoxides of Ch18:2, ie, Ch18:2-O(O)H. The distribution of apolipoproteins was more heterogeneous than that in the corresponding lipoproteins isolated from blood, and the majority of material in all plaque density fractions was present in large particles eluting in the void volume of gel-filtration columns. The content of unesterified cholesterol per unit of protein in low- and high-density fractions was 10-fold that in corresponding plasma lipoproteins. Low- and very-low-density fractions contained most of the lesion lipids and alpha-TOH. Two to five percent of lesion Ch18:2 was present as Ch18:2-O(O)H and distributed more or less equally among all density fractions, yet the content of alpha-TOH per unit of Ch18:2 was higher than that in corresponding plasma lipoproteins. These results demonstrate that alpha-TOH and oxidized lipids coexist in all lesion density fractions, further supporting the notion that large proportions of lipids in lipoproteins of advanced stages of atherosclerosis are oxidized. However, although not ruling it out, our results do not support the suggestion that advanced stages of atherosclerosis are associated with gross deficiencies in the lipoproteins' vitamin E content.
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PMID:Coexistence of oxidized lipids and alpha-tocopherol in all lipoprotein density fractions isolated from advanced human atherosclerotic plaques. 1039 89


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