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)

Lysyl oxidase is the copper-dependent enzyme responsible for the normal cross-linking of both collagen and elastin which is necessary for their functional integrity. There is now strong evidence that this enzyme is vitamin-B6-dependent. The earliest visible lesion of atherosclerosis, commonly found in human neonatal coronary arteries and probably indicative of the location of future atherosclerotic plaques, is a focal splitting of the internal elastic lamina, the cause of which has hitherto remained unexplained. It is suggested that this lesion is the result of imperfect cross-linking of arterial elastin as well as collagen, and is caused by a maternal deficiency of vitamin B6 which is commonly found in pregnancy and which could thus impair the function of lysyl oxidase. Prophylactic supplementation of maternal diet with adequate vitamin B6 is therefore suggested.
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PMID:The aetiological role of maternal vitamin-B6 deficiency in the development of atherosclerosis. 6 31

The association of copper with cardiovascular disease and a possible involvement of copper in the metabolism of cholesterol prompted the study on hypercholesterolemia mediated by copper deficiency. Copper deficient rats were found to exhibit a highly significant cholesterolemia (P less than 0.001), and plasma cholesterol showed a significant correlation with hepatic copper concentration (P less than 0.03). Two copper deficient rats died with hemothorax. The hearts of copper deficient rats were hypertrophied with large areas of hemorrhage, inflammation and focal necrosis. Prominent subendocardial fibroplasia was evident in copper deficient animals. The myocardial arteries of copper deficient rats were normal, however, aortas showed large areas of distorted and depleted elastic fibers. The results are discussed in terms of a possible role for copper in cholesterol metabolism, and in the pathogenesis of atherosclerosis.
Atherosclerosis 1978 Jan
PMID:Cholesterolemia and cardiovascular abnormalities in rats caused by copper deficiency. 62 27

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

The antioxidant activities of 17-beta-estradiol (E2) and other steroid hormones were studied by determining their effect on copper-catalyzed (cell-free) and mononuclear cell-mediated oxidation of low-density lipoproteins (LDL), as measured by the production of thiobarbituric acid-reactive substances (TBARS). The oxidation of LDL increased linearly with copper concentrations ranging from 0 to 10 mumol/L. E2 at a concentration of 1 mumol/L inhibited LDL oxidation by 37% to 62% at the various concentrations of copper. In a time-course study, E2 at 1 mumol/L delayed the onset of LDL oxidation in the presence of 5 mumol/L copper. E2 (1 mumol/L) inhibited TBARS production catalyzed by 5 mumol/L copper by 54%, compared with 60% inhibition by 1 mumol/L butylated hydroxytoluene (BHT), a known inhibitor of lipid peroxidation. Estriol at 5 mumol/L decreased LDL oxidation by 49%. Dehydroepiandrosterone (DHEA), testosterone, and estrone had no significant effects. E2 was also an effective inhibitor of mononuclear cell (MNC)-mediated oxidation of LDL, but had no effect on superoxide production by these cells. The onset of TBARS formation from cell-mediated LDL oxidation was also delayed by incubation with 1 mumol/L E2. The results indicate that estrogen may protect against atherosclerosis by inhibiting lipoprotein oxidation.
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PMID:The inhibition of low-density lipoprotein oxidation by 17-beta estradiol. 132 22

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

Oxidative modification of LDL renders it immunogenic and autoantibodies to epitopes of oxidised LDL, such as malondialdehyde (MDA)-lysine, are found in serum and recognise material in atheromatous tissue. However, there has been no prospective study to assess the importance of oxidised LDL among patients with vascular disease. We compared the titre of autoantibodies to MDA-modified LDL and native LDL in baseline serum samples of 30 eastern Finnish men with accelerated two-year progression of carotid atherosclerosis and 30 age-matched controls without progression. Neither group had specific antibody binding to native LDL. A titre was defined as a ratio of antibody binding to MDA-LDL/binding to native LDL. Cases had a significantly higher titre to MDA-LDL (2.67 vs 2.06, p = 0.003). Cases also had a greater proportion of smokers (37% vs 3%), higher LDL cholesterol (4.2 mmol/l vs 3.6 mmol/l), and higher serum copper concentration (1.14 mg/l vs 1.04 mg/l). Even after adjusting for these variables and the severity of baseline atherosclerosis, the difference in antibody titre remained significant in a multifactorial logistic model (p = 0.031). Thus, the titre of autoantibodies to MDA-LDL was an independent predictor of the progression of carotid atherosclerosis in these Finnish men. Our data provide further support for a role of oxidatively modified LDL in atherogenesis.
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PMID:Autoantibody against oxidised LDL and progression of carotid atherosclerosis. 135 50

Animal studies indicate a possible role for lipid oxidation in the development of atherosclerosis. We set out to investigate whether there was a relation between the ability of low-density lipoprotein (LDL) to resist oxidation in vitro and the severity of coronary atherosclerosis in man. 35 unselected young (mean [SD] age 39.9 [4.2] years) male survivors of myocardial infarction underwent angiography, and LDL was isolated from their plasma by density gradient ultracentrifugation. In-vitro LDL susceptibility to oxidation was assessed by determination of the lag phase for the formation of conjugated dienes in the presence of copper ions. An inverse relation was found between lag phase and quantitative estimates of global coronary atherosclerosis (r = -0.45; p less than 0.02). Multivariate analysis indicated that the lag phase for oxidative modification of LDL and LDL cholesterol concentration correlated independently with severity of coronary atherosclerosis. The lag phase for oxidation of LDL was also related to the triglyceride content of the LDL fraction (r = -0.55; p less than 0.002). The finding that susceptibility to LDL oxidation is associated with severity of coronary atherosclerosis may indicate that lipid oxidation promotes premature coronary atherosclerosis and that individuals with an LDL enriched in triglycerides are at particular risk.
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PMID:Susceptibility to low-density lipoprotein oxidation and coronary atherosclerosis in man. 135 86

The effects of propranolol, pindolol and metoprolol on the modification of low density lipoprotein (LDL) by U937 monocyte-like cells, endothelial cells and copper ions were studied by determination of the lipid peroxidation product content and measurement of the relative electrophoretic mobility of the particle. Propranolol and pindolol inhibited LDL oxidation by U937 cells in a dose-dependent manner from 10 to 100 microM, whereas metoprolol had no effect. In the case of LDL modification by endothelial cells, all the three beta-blockers were efficient within the same range of concentrations, and the order of potency was propranolol greater than pindolol greater than metoprolol. In vitro oxidation of LDL in the presence of copper ions was also inhibited by propranolol; pindolol and metoprolol had no significant protective effect in this system. These results concerning the inhibitory action of beta-blockers were confirmed by testing the degradation of modified LDL by J774 macrophages. Although the concentrations of the drugs utilized in this study are relatively high, in long-term treatment beta-blockers might accumulate in target tissues, and the protective effect of propranolol against LDL oxidation might be involved in its inhibitory action on atherosclerosis previously reported in animal models.
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PMID:Lipophilic beta-blockers inhibit monocyte and endothelial cell-mediated modification of low density lipoproteins. 135 72


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