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)

Siderophores, defined as high affinity iron(III) ion transport agents, and their cognate membrane-bound receptor complexes, occur in the enteric bacteria Escherichia coli and Salmonella typhimurium. The total system is tightly regulated by iron repression. The transport properties of the specific siderophores enterobactin and ferrichrome (which is not made by these particular enteric bacteria) have been examined in detail. In E. coli the outer membrane receptor for ferrichrome is programmed by the tonA gene; the receptor also serves as the binding site for T1, T5, phi80, albomycin and colicin M. Similarly, in S. typhimurium phage ES18, ferrichrome and albomycin compete for the genetic equivalent of the tonA locus. The ability of ascorbic acid to protect against atherosclerosis as well as rhinovirus infection in humans may be related to the role of the vitamin in iron metabolism. Deferrisiderophores are clinically useful in the treatment of acute and chronic iron poisoning but, on the other hand, they could constitute a natural hazard by transporting actinides, such as 239Pu, through the food chain.
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PMID:Siderophores: diverse roles in microbial and human physiology. 14 37

The activity of collagen prolyl hydroxylase in aortic wall was studied in rabbits exposed to chronic 10% ambient oxygen tension for 30 days. Prolyl hydroxylase in rabbit aorta was shown to be similar to the enzyme from other sources in that it required molecular oxygen, alpha-ketoglutarate, ferrous iron and ascorbate for its activity. The activity of prolyl hydroxylase was increased to 180% of controls in the intima-media samples from rabbits exposed to hypoxia. No atherosclerotic lesions could be seen in arteries of animals kept in chronic hypoxia. If the arteries of rabbits were injured with a single mechanical dilatation, the activity of prolyl hydroxylase increased more than 2-fold, as reported previously. The exposure of these animals to chronic hypoxia further elevated the prolyl hydroxylase activity.
Atherosclerosis 1979 Aug
PMID:Increased collagen prolyl hydroxylase activity in the aortic wall of rabbits exposed to chronic hypoxia. 22 78

The efficacy of an anion-exchange gel, Secholex, as a hypocholesterolemic agent was assessed in 46 patients in 4 different studies and the effects were compared with those of cholestyramine. All patients had severe Type II-a or II-b hyperlipoproteinemia. In short-term metabolic studies Secholex (15 g/day) and cholestyramine (16 g/day) decreased serum cholesterol levels and increased total fecal sterol output and serum methyl sterol concentration to a similar extent, but cholestyramine was more effective than Secholex in increasing fecal bile acid excretion. In crossover studies, the two drugs appeared to be equally effective in lowing serum cholesterol levels but the patients mostly preferred Secholex. Twenty patients were treated with Secholex over a two-year period. The average decrease in serum cholesterol levels from the mean pretreatment value of 406 mg/100 ml was 15% during the first year, and 13% during the second year. In 5 patients the serum cholesterol was permanently lowered by more than 20% (good responders), while in 7 patients the average reduction of serum cholesterol level during Secholex administration was less than 10% (non-responders). The serum triglyceride level was slightly decreased by Secholex in Type II-b patients but was unaltered in Type II-a patients. At the end of the treatment period, serum iron and vitamin B12 levels were normal but the serum folic acid concentration was reduced in eight of 20 patients. A dose--response study indicated that a similar cholesterol-lowering effect was obtained with daily doses of 9 and 15 g of Secholex. It is concluded that Secholex is a relatively safe drug which effectively reduces serum cholesterol levels in two-thirds of patients with severe hypercholesterolemia.
Atherosclerosis 1976 Sep
PMID:Treatment of hypercholesterolemia with Secholex. A long-term clinical trial and comparison with cholestyramine. 97 43

Trace metal contents of cerebral vessels in age-matched and sex-matched subjects from three population groups were estimated. The trace metals included calcium, manganese, zinc, magnesium, copper and iron. The American blacks in Washington, D.C., who are ethnologically related to Nigerian Africans, have different patterns of trace metal contents in their cerebral vessels and the observed levels also differed in some respects from Minnesota Caucasians living in a similar environment. The greatest amounts of calcium, zinc, and copper were found in the vessels of American blacks while the greatest amount of magnesium was found in vessels of Minnesota Caucasians. There was no statistically significant difference in the manganese content of the cerebral vessels in three population groups. Nigerian Africans had the least amounts of copper and magnesium but had the highest iron content. A similar high level of iron was observed in the vessels of American blacks. Since it has been shown that American blacks have the most extensive and severe degree of atherosclerosis among the three population groups, it would appear that iron, calcium and manganese in the cerebral vessels may not directly relate to the severity of cerebral atherosclerosis. Relatively high levels of copper and magnesium, which were observed in the cerebral vessels of American blacks and Caucasians, may be of significance in the pathogenesis of cerebral atherosclerosis. The low levels of the trace metals in Nigerians may be protective. The possible role of zinc requires further studies.
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PMID:Trace metal content of cerebral vessels in American Blacks, Caucasians and Nigerian Africans. 119 34

Insufficiencies of the circulatory system and increasing transport losses in pigs as well as analogies with respect to atherosclerosis of men and swine were the motives for a broad statistical investigation of important characteristics of the circulatory system in a big population of female German landrace pigs, fattened as progeny groups under identical conditions in a testing station and slaughtered at 100 kg weight. As the most essential results, highly significant seasonal and genetical influences on several traits are to be mentioned, and some meaningful correlations between them: Plasma cholesterol, ceruloplasmin and hematocrit showed markedly lower levels in the summer and increased values in the cold season; the thickness of the intima (aorta and arteria pulmonalis) was quite distinctly greatest in the spring, this phenomenon being almost exactly paralleled by augmented amounts of copper and iron in the aortic wall. Increased heart weights were again found in the cold, decreased ones in the warm seasons. On average, bigger hearts and vessels were accompanied by higher elastin contents of the aorta, but these contents stood in very significant negative correlation to the ash content and the amounts of certain mineral components (Ca, Mg and P) of the vessel wall, especially to the ash percentage of the elastic fibers. This indicates that calcifying and mineralizing processes in the wall obviously take place at the cost of the elastic components. The estimation of heritabilities in half and full sibs revealed with h2 = 60% high henetic influences on the elastin content of the aorta and equally so on the ash percentage of elastic fibers. Future investigations must correlate these findings with direct measurements of biomechanical and rheological properties of the vessels.
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PMID:[The exogenous and genetic components of some vessel wall characteristics in the pig (author's transl)]. 122 Jun 64

The content of 10 trace elements was studied by employing the neutron-activation method and the lead level determined through the spectral analysis in the whole blood, aorta, the heart muscle, liver, intesties (small and large), in the pancreas, adrenal glands, the spleen, lungs of accident victims, among whom 87 were practically healthy and 91 had atherosclerosis. The latter demonstrated in a number of organs (especially in the aorta and liver) a reduction in the content, which increased with age and intensity of atherosclerotic changes, of nickel, manganese, zinc, cobalt, vanadium and iron and rise in the lead, gallium, copper, bismuth and bromine level. The disclosed data bear witness to a definite part played by a number of trace elements in the atherogenesis.
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PMID:[Trace element content in the blood and organs in arteriosclerosis]. 123 10

Lipid peroxidation within human arterial lesions is thought to play an important role in the development of atherosclerosis. Peroxidation can be accelerated by the presence of 'catalytic' iron or copper ions. Gruel samples from advanced atherosclerotic lesions in the abdominal aortae of human cadavers were tested for pro-oxidant properties. All samples contained bleomycin-detectable iron and phenanthroline-detectable copper. Almost all gruel samples stimulated peroxidation of rat liver microsomes, and this was usually inhibited by the iron-ion chelator desferrioxamine. Some samples stimulated formation of hydroxyl radicals from H2O2 in the presence of ascorbate, a reaction again inhibited by desferrioxamine. We conclude that the interior of human advanced atherosclerotic lesions is a highly pro-oxidant environment, and that the use of copper or iron ions to promote peroxidation of low-density lipoproteins in vitro may be a valid model for events in the arterial wall.
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PMID:Stimulation of lipid peroxidation and hydroxyl-radical generation by the contents of human atherosclerotic lesions. 132 21

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

In the present study performed on rats, we investigated the influence of an in vivo acute iron load on several platelet parameters and their modification after vitamin E supplementation. Iron load was achieved by injecting iron dextran corresponding to 0.1 mg Fe3+ per kg in the gluteus muscles. Control rats were injected with an equal amount of a dextran solution. Analyses were performed 18 h after injection. By comparison with controls, in iron-injected animals, we found significant increases of: (1) serum total iron (by 110%); (2) aggregation of isolated platelets induced by low concentration of thrombin and ADP (by 350% and 120%, respectively); (3) thrombin-induced endogenous serotonin secretion (by 94%). We also studied the mobilization of radiolabeled arachidonate preincorporated into platelet phospholipids. The results indicated that the thrombin-stimulated release of arachidonate and formation of cyclooxygenase and lipoxygenase products (particularly thromboxane B2), were significantly increased. We also found in plasma an increase (by 67%) of malondialdehyde (MDA) as well as a decrease of vitamin E (by 60%). When vitamin E was injected the day before iron injection, platelet hyperactivity and thromboxane biosynthesis were reduced as well as the plasma MDA concentration. Consequently, given the key role of calcium flux in the activation processes in platelets, we also investigated the thrombin-induced Ca2+ uptake by means of radiocalcium. We found that in platelets from iron-treated rats the Ca2+ uptake amounted to 3670 +/- 201 pmol/10(9) platelets (plt) and was significantly different from controls (1680 +/- 192 pmol/10(9) plt, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1992 Oct
PMID:Effect of vitamin E on acute iron load-potentiated aggregation, secretion, calcium uptake and thromboxane biosynthesis in rat platelets. 146 49

Phagocyte-mediated oxidant damage to vascular endothelium is likely involved in various vasculopathies including atherosclerosis and pulmonary leak syndromes such as adult respiratory distress syndrome. We have shown that heme, a hydrophobic iron chelate, is rapidly incorporated into endothelial cells where, after as little as 1 h, it markedly aggravates cytotoxicity engendered by polymorphonuclear leukocyte oxidants or hydrogen peroxide (H2O2). In contrast, however, if cultured endothelial cells are briefly pulsed with heme and then allowed to incubate for a prolonged period (16 h), the cells become highly resistant to oxidant-mediated injury and to the accumulation of endothelial lipid peroxidation products. This protection is associated with the induction within 4 h of mRNAs for both heme oxygenase and ferritin. After 16 h heme oxygenase and ferritin have increased approximately 50-fold and 10-fold, respectively. Differential induction of these proteins determined that ferritin is probably the ultimate cytoprotectant. Ferritin inhibits oxidant-mediated cytolysis in direct relation to its intracellular concentration. Apoferritin, when added to cultured endothelial cells, is taken up in a dose-responsive manner and appears as cytoplasmic granules by immunofluorescence; in a similar dose-responsive manner, added apoferritin protects endothelial cells from oxidant-mediated cytolysis. Conversely, a site-directed mutant of ferritin (heavy chain Glu62----Lys; His65----Gly) which lacks ferroxidase activity and is deficient in iron sequestering capacity, is completely ineffectual as a cytoprotectant. We conclude that endothelium and perhaps other cell types may be protected from oxidant damage through the iron sequestrant, ferritin.
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PMID:Ferritin: a cytoprotective antioxidant strategem of endothelium. 151 45


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