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)

The generation of toxic oxygen metabolites is more usually associated with inflammation. However, pathological free radical reactions can cause tissue damage by adversely affecting prostacyclin (PGI2) synthesis allowing initiation of coagulation. We have assessed changes in the red cell defence to toxic oxygen metabolite generation, viz measurement of glutathione concentration (GSH) and superoxide dismutase activity (SOD). GSH and SOD were measured in 20 patients with peripheral arterial disease, 22 patients with vasculitis, and 11 patients with angina, and compared to 17 matched controls. The 53 subjects with arterial disease had significantly lower SOD levels: in contrast GSH levels were significantly higher. Extracellularly plasma thiol levels (PSH) were low and caeruloplasmin (Cp) levels were high. We suggest that free radical pathology exists not only in inflammatory vascular disease but also in atherosclerosis.
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PMID:Free radical pathology in chronic arterial disease. 270 21

As part of a study to determine the effect of 150 mg zinc/day on plasma lipoproteins, healthy young female (n = 26; mean age 27 years) and male (n = 21; mean age 28 years) volunteers took part in a double-blind cross-over trial lasting 12 weeks. During 6 weeks of supplementation, plasma Zn rose significantly in both groups, indicating compliance. Plasma total cholesterol remained unchanged in both males and females. However, mean LDL-cholesterol decreased from 2.38 to 2.17 mmol/l in females and there was a trend for total HDL-cholesterol to be redistributed in that HDL2 rose and HDL3 fell slightly. In parallel with these changes in females, Zn supplements reduced the ferroxidase activity of serum caeruloplasmin (from 13.0 to 11.3 U/ml) and the antioxidant activity of erythrocyte superoxide dismutase (E-SOD) (from 4557 to 3638 U/g Hb) and CuZn E-SOD (from 2184 to 1672 U/g Hb). Plasma Cu and haematocrit were unaffected. No such changes were seen in males in either lipoproteins or these indicators of Cu status. Since the females were lighter than the males but received the same dose, a dose-response effect rather than a sex difference cannot be ruled out. Overall, Zn supplements significantly decrease a major risk factor for CHD in females but reduced their Cu status.
Atherosclerosis 1988 Apr
PMID:The effect of zinc supplements on lipoproteins and copper status. 336 92

We have examined whether the toxic effects of homocysteine on cultured endothelial cells could result from the formation and action of hydrogen peroxide. In initial experiments with a cell-free system, micromolar amounts of copper were found to catalyze an oxygen-dependent oxidation of homocysteine. The molar ratio of homocysteine oxidized to oxygen consumed was approximately 4.0, which suggests that oxygen was reduced to water. The addition of catalase, however, decreased oxygen consumption by nearly one-half, which suggests that H2O2 was formed during the reaction. Confirming this hypothesis, H2O2 formation was detected using the horseradish peroxidase-dependent oxidation of fluorescent scopoletin. Ceruloplasmin was also found to catalyze oxidation of homocysteine and generation of H2O2 in molar amounts equivalent to copper sulfate. Finally, homocysteine oxidation was catalyzed by normal human serum in a concentration-dependent manner. Using cultured human and bovine endothelial cells, we found that homocysteine plus copper could lyse the cells in a dose-dependent manner, an effect that was completely prevented by catalase. Homocystine plus copper was not toxic to the cells. Specific injury to endothelial cells was seen only after 4 h of incubation with homocysteine plus copper. Confirming the biochemical studies, ceruloplasmin was also found to be equivalent to Cu++ in its ability to cause injury to endothelial cells in the presence of homocysteine. Since elevated levels of homocysteine have been implicated in premature development of atherosclerosis, these findings may be relevant to the mechanism of some types of chronic vascular injury.
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PMID:Endothelial cell injury due to copper-catalyzed hydrogen peroxide generation from homocysteine. 351 79

In a placebo-controlled trial healthy volunteers and patients with hyperlipoproteinemias types II and IV received orally vitamin E at doses of 300 mg and 600 mg daily for 2 weeks. Serum tocopherol levels increased two-fold, but serum concentrations of total lipids, cholesterol, triglycerides, ceruloplasmin and transferrin remained unchanged. Dietary supplementation with vitamin E suppressed elevated concentrations of plasma lipid peroxides and this effect was correlated with an increase in serum antioxidant activity. In patients a mild platelet suppressant effect of vitamin E (600 mg daily) was observed. Feeding an atherogenic diet to rabbits for a week resulted in elevation of plasma lipid peroxides and a 90% decrease in arterial generation of prostacyclin. Enrichment of the atherogenic diet with 100 mg vitamin E daily prevented the increase in plasma lipid peroxides and protected the prostacyclin generating system in arteries. Thus, in hyperlipoproteinemias vitamin E corrects certain abnormalities of lipid metabolism which might predispose to atherosclerosis.
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PMID:Dietary supplementation with vitamin E in hyperlipoproteinemias: effects on plasma lipid peroxides, antioxidant activity, prostacyclin generation and platelet aggregability. 390

Serum proteins and lipoproteins were determined in 23 menopausal females after surgery for early forms of breast cancer and the results compared with data from a matched group of randomly selected healthy females. The patients were randomly divided into 2 groups, one serving as a control group, the other receiving 40 mg tamoxifen daily for 2 months. Breast cancer patients were found to have significantly higher concentrations of serum cholesterol than controls (7.90 +/- 1.15 vs. 6.87 +/- 1.18 mmol/l, P less than 0.001), which was the result of a 16% higher concentration in LDL cholesterol (P less than 0.05) and a 13% higher concentration in HDL cholesterol (P less than 0.05). During tamoxifen therapy total TG tended to increase, whereas total cholesterol fell. Significant lipoprotein changes were found in the LDL fraction where LDL-TG increased from 0.46 to 0.56 (P less than 0.01) and LDL cholesterol fell from 5.11 to 4.10 mmol/l (P less than 0.001). During tamoxifen therapy haptoglobin and orosomucoid concentrations fell significantly (P less than 0.01), whereas those of alpha-antitrypsin and ceruloplasmin increased (P less than 0.001). Factors such as diet and weight may explain the differences between breast cancer patients and controls. The tamoxifen-induced changes indicate that this anti-oestrogen exerted a mild oestrogen-like effect with regard to protein and lipoprotein metabolism.
Atherosclerosis 1984 Sep
PMID:Serum lipoproteins and proteins after breast cancer surgery and effects of tamoxifen. 649 36

Calcium, magnesium, copper and zinc were determined in serum in men with femoral atherosclerosis. Also total cholesterol, HDL- and LDL-cholesterol were estimated. Subjects in control group were in the same range of age. The present study compares two methods of preparing serum for the flame atomic absorption spectrometry. In the first method (I), serum was diluted by the demineralized water. In the second method (II), serum protein was precipitated by trichloracetic acid (TCA). We found that the first method (I) was simpler and more precise than the other. The optimal proportions of serum and water amounted to 1 + 62 for calcium and magnesium and the coefficient of variation (C.V.) was 2.8%. For copper and zinc, the optimal dilution was 1 + 3 (C.V. = 1%). Total cholesterol was significantly higher (p < 0.05) and HDL-cholesterol was lower (p < 0.05) in subjects with femoral atherosclerosis as compared with controls. There was no difference in LDL-cholesterol. Subjects with femoral atherosclerosis had significantly higher level of all micro- and macroelements determined, then those of the control group (p < 0.05). However, higher serum copper does not necessary mean higher copper body status. It is possible that higher serum copper in femoral atherosclerosis reflects the transfer of copper from the tissue to the ceruloplasmin, as an acute phase reaction. On the other hand, the differences in serum magnesium, calcium, copper and zinc concentrations, may indicate the possible involvement of these elements in the disorder of total and HDL-cholesterol in femoral atherosclerosis.
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PMID:[Calcium, magnesium, copper and zinc in blood serum in men with femoral atherosclerosis]. 748 5

Low density lipoprotein (LDL), if it becomes oxidized, develops several unique properties including the capacity to provoke endothelial cytotoxicity via metal-catalyzed free radical-mediated mechanisms. As were previously have shown that iron-catalyzed oxidant injury to endothelial cells can be attenuated by the addition of exogenous iron chelators such as the lazaroids and deferoxamine, we have examined whether the endogenous iron chelator, ferritin, might provide protection from oxidized LDL. LDL oxidized by iron-containing hemin and H2O2 is toxic to endothelial cells in a time- and dose-dependent fashion. Endothelial cell ferritin content is increased by pretreatment of cells with iron compounds or by the direct addition of exogenous apoferritin; ferritin-loaded cells are markedly resistant to the toxicity caused by oxidized LDL. Iron inactivation by ferritin depends on its ferroxidase activity. When a recombinant human ferritin heavy chain mutant, 222, which is devoid of ferroxidase activity, is added to endothelial cells, unlike the excellent protection afforded by the wild-type recombinant heavy chain, endothelial cells are not protected from oxidized LDL. To assess the in vivo relevance of our observation, we examined human coronary arteries of cardiac explants taken from patients with end-stage atherosclerosis. Large amounts of immunoreactive ferritin are focally detected in atherosclerotic lesions, specifically in the myofibroblasts, macrophages, and endothelium without a notable increase in Prussian blue-detectable iron. These findings suggest that ferritin may modulate vascular cell injury in vivo.
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PMID:Ferritin protects endothelial cells from oxidized low density lipoprotein in vitro. 767 89

The relation of serum glycoproteins and C-reactive protein (CRP) to severity of coronary atherosclerosis was examined in 133 men and 92 women undergoing coronary angiography. The following serum glycoproteins were determined: alpha 1-antitrypsin, alpha 1-acid glycoprotein, alpha 2-macroglobulin, ceruloplasmin, haptoglobin, fibrinogen, C4b binding protein, and lipoprotein (a) [Lp(a)]. Sex- and age-adjusted levels of alpha 1-antitrypsin, alpha 1-acid glycoproteins, alpha 2-macroglobulin, ceruloplasmin, Lp(a) and CRP were significantly associated with the severity of coronary atherosclerosis as determined by the Gensini score; these associations remained significant even after adjustment for body-mass index, smoking history, hypertension, and total cholesterol, except for Lp(a) (p = 0.075). These findings suggest that certain serum glycoproteins and CRP can serve as independent indicators for the progression of coronary atherosclerosis.
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PMID:Serum glycoproteins and severity of coronary atherosclerosis. 783 94

LDL oxidation within the arterial wall may contribute to the disease of atherosclerosis. There is some evidence that elevated plasma levels of copper are associated with an increased risk of coronary artery disease. We have investigated the conditions under which caeruloplasmin (the plasma copper carrier protein) can catalyse the macrophage-mediated modification of LDL. Low concentrations of CuSO4 (< 1 microM) could catalyse the macrophage-mediated modification of LDL. Native caeruloplasmin was unable to catalyse the modification of LDL at pH 7.4, but could do so after preincubation at acidic pH. After preincubation at acidic pH, concentrations of caeruloplasmin as low as 30 micrograms/ml (about one-tenth of the human plasma level) could catalyse significant LDL oxidation when added to macrophages. The activation of copper in caeruloplasmin in atherosclerotic lesions due to a localised acidic pH may help to explain why LDL oxidation occurs in these areas of the body.
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PMID:Acidic pH enables caeruloplasmin to catalyse the modification of low-density lipoprotein. 830 68

It has been suggested that the increase in concentration of blood lipid peroxides may be a risk factor for atherosclerosis. Our research was conducted to study the effect of cholesterol feeding on lipid peroxides, ceruloplasmin, HDL-cholesterol, serum unesterified fatty acids, and copper concentration in serum and aortic tissue in rats. In the animals fed a cholesterol-supplemented diet, the mean values of serum lipid peroxide, ceruloplasmin, serum copper, and unesterified fatty acids were increased significantly (p < 0.01) as compared to the control group. At the same time, HDL-cholesterol concentration was significantly decreased in rats fed a diet enriched with cholesterol (p < 0.01) compared to the control group. A significant decrease of copper concentration in aorta was also observed in these animals versus controls. Correlations between ceruloplasmin and lipid peroxides as well as copper were statistically significant in these animals. At the same time, antioxidant activity in blood was two times higher as compared to controls. Results of this study provide the support for applying these determinations in atherosclerosis monitoring.
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PMID:Free radicals, ceruloplasmin, and copper concentration in serum and aortic tissue in experimental atherosclerosis. 874 29


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