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 relationship of lipoperoxidemia and HDL-cholesterolemia to circulating zinc and copper was investigated in patients undergoing chronic hemodialysis. When the serum zinc level was low and the copper level was high, or when the zinc, copper ratio was low, decreased concentrations of HDL-cholesterol were observed. In view of the high incidence of atherosclerosis among patients undergoing chronic hemodialysis, zinc and copper may somehow contribute to atherogenesis by affecting the serum HDL-cholesterol concentrations.
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PMID:Probable atherogenic role of zinc and copper as studied in chronic hemodialysis patients. 717 74

Serial liver biopsies were carried out in 67 patients with HLP and/or fatty liver before, during short- and long-term therapy with CPIB and after termination of therapy. Results (1) Decrease of liver glycogen from 4.17% to 2.69% (wet weight, P less than 0.02). (2) Insignificant changes of liver triglyceride content. (3) Significant decrease of manganese, while the concentrations of zinc and copper in the liver biopsy specimens remained unchanged. (4) No signs of liver intoxication or cancerogeneous effects of light-microscopic pictures. (5) Significant increases in numbers of mitochondria and cristae as well as a hypertrophy of endoplasmic reticulum with longer lasting therapy. (6) Striking focal proliferation of cristae mitochondriales in 3 cases on longterm treatment. (7) Regression of the mitochondrial alterations after termination of the CPIB therapy. Our findings suggest that an increased number of mitochondria and of their inner membranes in the liver cells induced by CPIB could play an important role in the hypolipidemic action of the drug.
Atherosclerosis 1980 Jun
PMID:Effects of p-chlorophenoxyisobutyric acid (CPIB) on the human liver. 740 47

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

The oxidation of low-density lipoprotein (LDL) may be important in the pathogenesis of atherosclerosis. However, the interactions between cells and metals in promoting LDL oxidation are inadequately understood. A sensitive high-performance liquid chromatography analysis of cholesterol, cholesteryl esters, and their oxidation products was used to identify and accurately measure LDL oxidation achieved in thiol-free Hanks' balanced salt solution (HBSS) at pH 7.4. Mouse peritoneal macrophages inhibited LDL oxidation when incubated in HBSS containing either 10 microM iron or 1 microM copper, but were markedly prooxidant in the presence of both metals. The prooxidant effect of macrophages in the presence of both iron and copper did not require the provision of added disulfides or thiols. Both Fe2+ and macrophages were demonstrated to independently reduce Cu2+ to Cu1+ in HBSS, indicating that the direct reduction of copper by cells or iron may underlie the observed promotion of LDL oxidation by macrophages in this system. We conclude that macrophages can either promote or inhibit metal-mediated LDL oxidation and that externally supplied thiols are not essential to the promotion of LDL oxidation by cells. The presence of both iron and copper may be particularly important for macrophages to promote LDL oxidation in vivo.
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PMID:Macrophages require both iron and copper to oxidize low-density lipoprotein in Hanks' balanced salt solution. 748 58

In spite of the pathological significance of oxidation of plasma lipids, no method is currently available for the evaluation of the susceptibility of these lipids to oxidation in unfractionated plasma. Here we demonstrate that copper-induced oxidation of diluted plasma, in the presence of citrate can be monitored continuously by recording the absorbance at 245 nm. The kinetics of accumulation of oxidation products in unfractionated plasma is a sum of lipid oxidation products obtained in low and high density lipoproteins isolated from the same plasma. The kinetic profiles are reproducible and can be performed with plasma samples even after prolonged storage at 4 degrees C (up to two months) or after freezing and thawing of the plasma. Being simple and reproducible, yet correlating with the oxidizability of low and high density lipoproteins, this method can be used to evaluate the "oxidation resistance" of plasma lipids and thus serve as a standard index of the susceptibility of the plasma lipids of patients to oxidation-inflicted pathologies, including atherosclerosis.
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PMID:Copper-induced lipid oxidation in unfractionated plasma: the lag preceding oxidation as a measure of oxidation-resistance. 748 4

We examined the interactive effect of oxidized low density lipoprotein (LDL) and ascorbic acid on collagen production in cultured smooth muscle cells (SMCs). Porcine aortic SMCs were incubated with 50-200 micrograms/ml of human LDL with/without 5 microM Cu2+ for 24 h. Collagen production was assayed by successive salt precipitation at acidic and neutral pH after pepsin digestion of 3H-proline-labeled collagenous protein. Oxidation of LDL was evaluated by electrophoresis and by the level of thiobarbituric acid reactive substances (TBARS). Ascorbic acid reduced the oxidation of LDL + Cu2+ (53% reduction). In the presence of ascorbic acid, no differences were noted in collagen production between LDL and LDL + Cu2+. Without ascorbic acid, collagen production with LDL + Cu2+ was increased dose-dependently up to 6-fold with 150 micrograms/ml LDL, while no such effects were observed at any doses of native LDL. The addition of butylated hydroxytoluene to LDL + Cu2+ strongly suppressed oxidation (88% reduction), and significantly reduced collagen production close to that seen with native LDL. These results indicate that oxidized LDL stimulates collagen production in SMCs, while native LDL does not. Therefore, oxidized LDL may play a direct role in stimulating collagen production in SMCs, which could lead to collagenosis in atherosclerosis.
Atherosclerosis 1995 Jul
PMID:Oxidized low density lipoprotein stimulates collagen production in cultured arterial smooth muscle cells. 748 30

In animals fed a hypercholesterolemic diet, development of atherosclerosis is preceded by attachment of mononuclear leukocytes to the arterial endothelium. Early lesions begin to develop as monocytes migrate into the intima and ingest lipids. A major part of these lipids is believed to be derived from oxidatively modified low density lipoprotein (LDL). In the present study we demonstrate that human mononuclear leukocytes exposed to low concentrations of copper-oxidized LDL secrete one or several factors that stimulate the expression of intercellular adhesion molecule-1 (ICAM-1, CD54), vascular cell adhesion molecule (VCAM-1) and endothelial selectin (E-selectin-1, ELAM-1), whereas native LDL was found to be without effect. Exposure of endothelial cells to non-conditioned medium containing oxidized LDL did not influence the expression of adhesion molecules. Incubation of endothelial cells with conditioned medium from mononuclear cells grown in the presence of oxidized LDL also resulted in a three-fold increase in the binding of monocytoid U937 cells. The present findings suggest that mononuclear leukocytes exposed to oxidatively modified LDL in early atherosclerotic lesions may stimulate the recruitment of other leukocytes by secreting cytokines which induce the expression of adhesion molecules on the endothelium.
Atherosclerosis 1993 Nov
PMID:Mononuclear leukocytes exposed to oxidized low density lipoprotein secrete a factor that stimulates endothelial cells to express adhesion molecules. 750 27

Blood specimens from twenty-six renal transplant recipients treated with cyclosporine (CsA) were collected at weekly intervals, two months after transplantation. Specimens were grouped according to their CsA concentrations. Group I consisted of ten specimens with CsA concentration of >400 ng/ml; group II consisted of ten specimens with CsA concentrations ranging from 120-300 ng/ml; and group III consisted of six specimens with CsA concentrations of < 100 ng/ml. In addition, specimens from five renal transplant patients who, instead of CsA, received the immunosuppressant FK506 (group IV), and from six healty individuals were included. Plasma low-density lipoproteins (LDL) were isolated and their susceptibility to oxidation was studied by continuously monitoring the formation of conjugated dienes during copper ion-mediated oxidation. Patients with higher blood concentrations of CsA (groups I and II) had significantly higher oxidizability of LDL, as indicated by the shorter time required to start the oxidation (lag phase). The oxidizability of samples with low concentration of CsA (group III) was not significantly different from that of FK506-treated patients or healthy individuals. There was a negative correlation (r = -0702, P < 0.01) between oxidizability (lag phase) and CsA concentration in LDL. No correlation between blood CsA and plasma cholesterol or triglyceride concentration was evident during a three-month period postoperatively. Similarly, no correlation between the degree of oxidizability and plasma cholesterol or triglycerides was found at the time of the experiment. These findings suggest a prooxidant effect of CsA to plasma LDL, and may indicate that CsA is an important risk factor in the accelerated atherosclerosis of renal transplant recipients.
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PMID:Cyclosporine increases the oxidizability of low-density lipoproteins in renal transplant recipients. 752 2

An important characteristic of hyperlipaemia associated with magnesium deficiency in rats is the postprandial accumulation of triglyceride-rich lipoproteins (TGRLP). The present investigation was performed to determine the susceptibility of TGRLP isolated from magnesium-deficient rats to metal ion and cell dependent peroxidation and the effect of these lipoproteins on cultured vascular smooth muscle cells (VSMC). TGRLP were isolated by sequential ultracentrifugation from plasma of control and magnesium-deficient rats fed for 8 d on adequate or magnesium-deficient diets. Magnesium-deficient animals were hypertriglyceridemic as compared to control rats. After exposure to oxidative stress in vitro, Cu2+ or activated macrophages, conjugated diene production was significantly higher in TGRLP isolated from magnesium-deficient rats. Culture of VSMC with TGRLP from magnesium-deficient rats resulted in more important cell growth than with lipoproteins isolated from control animals. After incubation with VSMC, TGRLP from magnesium-deficient rats showed higher conjugated diene production than those from control rats. These results support the atherogenic properties of magnesium deficiency, which is accompanied by hyperlipaemia and which affects two important linked pathways in atherosclerosis, lipoprotein peroxidation and VSMC proliferation.
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PMID:Triglyceride-rich lipoproteins from magnesium-deficient rats are more susceptible to oxidation by cells and promote proliferation of cultured vascular smooth muscle cells. 754 76

Oxidative damage due to free radical production is increased in uraemic patients and has been suggested as a possible factor contributing to the anaemia of chronic renal failure (CRF) and the pathogenesis of atherosclerosis. Oxidative stress was assessed in 40 patients with CRF maintained by either haemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD) and in 18 healthy controls. Lipid peroxidation (assessed as malondialdehyde, MDA), total glutathione (TG), antioxidant enzyme (glutathione reductase (GSHRx), glutathione peroxidase (GSHPx) and superoxide dismutase (SOD)) activity and antioxidant associated trace metal (selenium, copper, zinc) levels were studied. Erythrocyte membrane fluidity was examined using the fluorescent probe 1,6 diphenyl-1,3,5-hexatriene (DPH). The results indicate increased levels of oxidative stress and altered erythrocyte membrane fluidity in patients treated with CAPD compared with controls and patients treated with HD. Only minor changes were observed in patients treated with HD. Altered free radical activity, oxidative stress and altered erythrocyte membrane fluidity observed in patients with CRF may contribute to the increase in vascular disease in such patients and to the anaemia of CRF.
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PMID:Oxidative stress and erythrocyte membrane fluidity in patients undergoing regular dialysis. 755 72


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