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

Accelerated atherosclerotic lesions are observed in genetic defects characterised by marked homocystinaemia as a result of low levels of cystathionine synthase, a pyridoxal phosphate-dependent enzyme. Attempts were therefore made to induce atherosclerosis in Macaca radiata, maintained on a high-protein, high-methionine and high-fat diet by inducing pyridoxine deficiency with deoxypyridoxine. Pyridoxine deficient monkeys failed to show any biochemical or pathological evidence of atherosclerosis, despite a significant decrease in the activity of hepatic cystathionine synthase.
Atherosclerosis 1977 Jul
PMID:Failure to produce atherosclerosis in Macaca radiata on a high-methionine, high-fat, pyridoxine-deficient diet. 90 21

Rabbits become hypercholesterolemic when transferred from commercial feed to a low fat, cholesterol-free semisynthetic diet. The role of different dietary components in mediating this effect was investigated by varying the composition of the semisynthetic diet and of the commerical feed. Addition of alfalfa to the semisynthetic diet prevented the normal hypercholesterolemic response, but other plant products, including several with high fibre content, were ineffective. Increasing the content of powdered cellulose appeared to enhance the response. A commercially formulated diet in which the alfalfa and soybean meal components were replaced by ground corn and oats did not produce a significant elevation of plasma cholesterol. Substitution of different sugars or starches for the dextrose in the semisynthetic diet gave variable results, but of those tested, only potato starch prevented the hypercholesterolemia. The type of protein used in the semisynthetic diet had a marked influence on the level of plasma cholesterol. Semisynthetic diets containing proteins from animal sources gave higher plasma cholesterol levels than those containing proteins from plant sources. Very low levels were obtained with a low choline semisynthetic diet containing soy protein isolate, and supplementation with choline and methionine only raised the level to that normally obtained with commercial feed. Replacement of the salt mixture in the semisynthetic diet by one specially recommended for rabbits made no significant difference to the hypercholesterolemic response. Prevention of coprophagy did not significantly affect plasma cholesterol levels in rabbits on either commerical or semisynthetic diets. Growth performance was generally better on commercial feed than on semisynthetic diets but there was no direct correlation between weight gain and level of plasma cholesterol in rabbits on the different semisynthetic diets.
Atherosclerosis
PMID:Plasma cholesterol levels in rabbits fed low fat, low cholesterol diets: effects of dietary proteins, carbohydrates and fibre from different sources. 94 88

Individuals with homocystinuria have been found to suffer from several types of inherited enzymatic deficiencies. Experiments indicated that vascular changes were subsequent to the metabolic effects of homocysteine derivatives in the tissues. Experimental studies in animals showed that homocysteine thiolactone, methionine, homocysteic acid, and homocystine cause fibrous arteriosclerotic plaques, arterial thrombosis or venous thrombosis with pulmonary embolism. The type which develops depends on the particular homocystine derivative, the dose, and the route of administration. The use of oral contraceptives causes similar alterations in nutrient metabolism. This fact suggests the possibility of increased risk of atherosclerosis, thrombosis, and embolism among long-term oral contraceptive users. Pyridoxine supplementation may reduce the risk. Further research is needed to assess the degree of risk involved.
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PMID:Homocystine, atherosclerosis and thrombosis: implications for oral contraceptive users. 109 78

Arteriosclerotic plaques were found in the aorta and arteries of rabbits given homocysteine thiolactone, methionine or homocysteic acid, both parenterally and in a synthetic diet. Animals given large doses of parenteral methionine or homocysteine thiolactone died of pulmonary embolism and pulmonary infarct. Pyridoxine prevented thrombosis and pulmonary embolism but did not prevent arteriosclerotic plaques. These findings and previous work, showing a new matabolic pathway for sulfate ester synthesis from methionine, the somatotrophic activity of homocysteic acid, and control of cellular growth and intercellular matrix synthesis by homocysteine derivatives, suggest a theory to explain aspects of the pathogenesis of arteriosclerosis.
Atherosclerosis
PMID:Homocysteine theory of arteriosclerosis. 119 72

It is well known that accumulation of methionine in the internal organs is weaker in animals with experimental atherosclerosis. On the basis of this concept the authors carried out studies on rabbits and guinea pigs with atherosclerosis, induced by cholesterol diet and treated with protein hydrolysate-hydropront in a dose of 5 ml/kg of body weight daily for rabbits and every two days for guinea pigs. Distribution of methionine 75Se was examined in the internal organs. The radioisotope in a dose of 5 microcurie was injected two hours before killing of the animals. There was a reduced accumulation of methionine 75Se in the internal organs of rabbits and guinea pigs with experimental atherosclerosis. The disturbances were increased after prolongation of cholesterol feeding. The application of protein hydrolysate considerably improved the accumulation of methionine in the treated animals compared with the untreated animals with atherosclerosis.
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PMID:[Distribution of methionine-75Se in animals with experimental atherosclerosis treated with a protein hydrolysate]. 122 4

Low density lipoprotein (LDL) oxidation mediated by phorbol myristate acetate (PMA)- and formylmethionylleucylphenylalanine (FMLP) -stimulated human neutrophils was enhanced by 70% in the presence of ferritin. Iron released from ferritin by the superoxide anion generated in the respiratory burst of stimulated neutrophils is shown to be involved in lipoprotein oxidation. Ascorbate (100 microM), superoxide dismutase (10 micrograms/ml) and uric acid (430 microM) showed inhibitory effects of 30% [corrected], 70% and 50% on LDL oxidation, respectively. Ceruloplasmin (2.7 microM) potentiated LDL oxidation by stimulated neutrophils and ferritin, both alone and in the presence of methionine. Methionine (1 mM) and catalase (30 micrograms/ml) increased LDL oxidation by stimulated neutrophils and ferritin. These data suggest that LDL oxidation by stimulated neutrophils and ferritin may be relevant in inflammation when both neutrophils and ferritin are increased.
Atherosclerosis 1992 Dec
PMID:Low density lipoprotein oxidation by stimulated neutrophils and ferritin. 133 54

Elevated plasma homocysteine enhances the risk of thrombosis and premature arteriosclerosis. We have assessed the activity of the 3 prime enzymes of homocysteine metabolism in cultured human venous endothelial cells, in a study of their possible protective roles. In cells from 4 individuals, cultured in Dulbecco's modified Eagle medium, the mean activity +/- S.D. of cystathionine beta-synthase (nmol of product/h per mg of cell protein, at 37 degrees C) was 3.58 +/- 3.11 at pH 8.6. The assay used was our newly developed amino acid analyser-based procedure. The activity of 5-methyltetrahydrofolate:homocysteine methyltransferase at pH 7.4 was 4.12 +/- 1.25 and betaine:homocysteine methyltransferase (BHMT) was undetectable (< 1.4 nmol/h per mg protein). Cells were also cultured in a medium aimed at stimulating methionine biosynthesis, containing methionine-deficient Dulbecco's modified Eagle medium to which L-homocystine (100 mumol/l) and methylcobalamin (1 mumol/l) had been added. In these cells 5-methyltetrahydrofolate:homocysteine methyltransferase activity increased to 7.95 +/- 1.45, P < 0.001, there was a non-significant decrease in cystathionine beta-synthase activity to 2.16 +/- 1.52 and BHMT activity was still undetectable. These cells were more resistant to in vitro homocysteine-induced detachment than were cells from the same line cultured in Dulbecco's modified Eagle medium alone. Our findings establish that human endothelial cells express 2 of the 3 primary enzymes of homocysteine catabolism. They suggest that persons who are deficient in cystathionine beta-synthase or 5-methyltetrahydrofolate:homocysteine methyltransferase activity may not only develop homocysteinemia, but also have vascular endothelium which is more susceptible to damage by homocysteine than persons with normal enzyme levels.
Atherosclerosis 1992 Nov
PMID:Homocysteine catabolism: levels of 3 enzymes in cultured human vascular endothelium and their relevance to vascular disease. 144 98

Hyperhomocysteinemia arising from impaired methionine metabolism, and usually due to a deficiency of cystathionine beta-synthase is a significant and independent risk factor for symptomatic vascular disease. It is not known if hyperhomocysteinemia in apparently healthy asymptomatic subjects is associated with atherosclerosis and whether such a relationship is independent of conventional risk factors. The prevalence of asymptomatic extracranial carotid artery atherosclerosis was determined by duplex ultrasound examination in 25 obligate heterozygotes with respect for cystathionine beta-synthase deficiency (whose children were known to be homozygous for this genetic defect) and in 21 controls. Hyperhomocysteinemia was determined by a standard methionine-loading test and conventional risk factors were also recorded. Twelve of 25 obligate heterozygotes and 8 of 21 normal controls had evidence of extracranial carotid artery atherosclerosis. Hyperhomocysteinemia as a genetic trait was not a significant risk marker, but the actual homocysteine level was associated with an increased risk of carotid disease. After adjustment for the effects of other significant risk factors, the odds ratio of hyperhomocysteinemia for carotid disease was 1.038 per unit increase in homocysteine level (P = 0.03). Hyperhomocysteinemia is a weak risk factor for asymptomatic extracranial carotid atherosclerosis and the relative risk associated with this genetic trait is less than that observed in a study of patients presenting with clinical manifestations of vascular disease.
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PMID:Hyperhomocysteinaemia: a risk factor for extracranial carotid artery atherosclerosis. 151 57

Absent hepatic lipase (HL) activity results in dyslipidemia and premature atherosclerosis. DNA sequencing of the HL gene from subjects with heritable HL deficiency identified a new C to T substitution within exon 8 that in the mature enzyme caused a threonine to methionine change at position 383 (T383M). With a rapid DNA detection method we observed that all 6 individuals with complete HL deficiency from 2 families had the T383M mutation. None of 50 random unrelated unaffected subjects had this mutation. We propose that T383M is specific to families with heritable HL deficiency. Furthermore, structural variation at the HL gene, possibly in combination with other factors, appears to be etiologic in HL deficiency.
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PMID:A hepatic lipase gene mutation associated with heritable lipolytic deficiency. 167 86

In rabbits with experimental atherosclerosis induced by a cholesterol-rich diet, alpha 1-antitrypsin concentration was decreased as compared with control, by 34%, whereas alpha 2-macroglobulin concentration was increased by 86%. In animals fed a methionine-rich diet changes in concentration of both inhibitors involved in elastase metabolism were but slight, if any.
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PMID:Concentration of some proteinase inhibitors: alpha 1-antitrypsin and alpha 2-macroglobulin in rabbit blood serum in two models of experimental atherosclerosis. 170 85


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