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

New atherosclerosis causative factors and preventive modalities have been identified. Atherogenic factors include lipid oxidation products, such as cholesterol oxidation products, malonaldehyde and other aldehydes; trans-fatty acids; some saturated fatty acids (lauric, myristic and possibly palmitic acids); and myristic acid plus cholesterol. Lipid oxidation products are well suited to induce arterial damage, based on their known cytotoxic effects; evidence also indicates the possibility of plaque promotion and stimulation of thrombogenesis. Anti-atherogenic factors include antioxidants, fish oils and other polyunsaturates (if protected from oxidation), fibre and trace minerals such as copper, manganese, selenium and zinc. Iron is unique, being considered as both a potential promoter of atherosclerosis (component of ferritin, conceivably inducing lipid oxidation) and a possible anti-atherogenic component (of antioxidant enzyme catalase). It is apparent that an entire new series of research challenges has been uncovered.
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PMID:Atherogenic and anti-atherogenic factors in the human diet. 866 Apr

We investigated the effect of lead nitrate (0.5-5.0 microM) on the repair of wounded monolayer of cultured bovine aortic endothelial cells. It was morphologically found that lead decreases the appearance of the cells in the wounded area in a concentration-dependent manner without degenerative changes after a 48-h incubation. Although mercury weakly inhibited the repair with nonspecific cell damage, the other cations including bismuth, cobalt, manganese and nickel failed to affect the repair. The inhibition of endothelial repair caused by lead was observed even when stimulated by exogenous either basic or fibroblast growth factor. These results indicated that inhibition of the repair process of damaged endothelial cell layer is a component of lead-induced vascular lesions such as atherosclerosis.
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PMID:Inhibitory effect of lead on the repair of wounded monolayers of cultured vascular endothelial cells. 905 98

The response to nitric oxide of intracellular free Ca2+ levels, measured by fura 2 fluorimetry, and cyclic GMP, measured by RIA, was evaluated on smooth muscle cells of the thoracic aorta in primary culture from normal and cholesterol-fed rabbits. Relaxation to acetylcholine and nitric oxide was also determined in isolated rings of aorta. After 10 weeks of high-cholesterol diet, the intact aorta relaxed less to both acetylcholine and nitric oxide. In cultured cells from hypercholesterolemic rabbits, intracellular Ca2+ oscillated, and the mean Ca2+ levels were approximately twofold greater than in normal aortic cells. Nitric oxide failed to affect basal Ca2+ in either cell type. The peak and sustained rise in intracellular Ca2+ induced by angiotensin II (10(-7) mol/L) were similar in the two cell types. However, nitric oxide (10(-10) to 10(-6) mol/L) decreased the sustained Ca2+ levels to a significantly smaller extent in cells from cholesterol-fed rabbits. In addition, in cells from hypercholesterolemic rabbits, nitric oxide added before angiotensin II inhibited to a smaller degree the transient increase in intracellular free Ca2+ caused by angiotensin II in the nominal absence of extracellular Ca2+, as well as the increase in Ca2+ associated with the addition of extracellular Ca2+. Measurements of fura 2 quenching caused by Mn2+ influx confirmed that nitric oxide inhibited the entry of extracellular divalent cations significantly less in cells from hypercholesterolemic rabbits. Basal levels of cyclic GMP were significantly less than normal, and nitric oxide increased levels of cyclic GMP to a significantly smaller degree in cells from cholesterol-fed rabbits. These data indicate a substantial resistance to nitric oxide action in aortic smooth muscle cells of cholesterol-fed rabbits. This observation is consistent with the notion that resistance of smooth muscle cells to nitric oxide contributes to abnormal endothelium-dependent vasodilation during hypercholesterolemia and can play a role in the pathogenesis of atherosclerosis.
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PMID:Reduced responsiveness of hypercholesterolemic rabbit aortic smooth muscle cells to nitric oxide. 908 96

We investigated the effect of zinc sulfate on the proliferation of cultured bovine aortic smooth muscle cells stimulated with or without growth factors. Zinc had no effect on the incorporation of [3H]thymidine into the acid-insoluble fraction of the cells stimulated with or without platelet-derived growth factor or transforming growth factor beta 1. However, it was shown that stimulation of the [3H]thymidine incorporation by either basic or acidic fibroblast growth factor was significantly potentiated by zinc. Other cations including copper, manganese and nickel did not exhibit such an activity. The present data suggest that zinc is a particular heavy metal which potentiates vascular smooth muscle cell proliferation stimulated by basic and acidic fibroblast growth factors as well as thrombospondin. Zinc may be involved in the intimal hyperplasia of atherosclerosis.
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PMID:Zinc potentiates the stimulation by basic and acidic fibroblast growth factors on the proliferation of cultured vascular smooth muscle cells. 950 72

Oxidation of LDL in the subendothelial space has been proposed to play a key role in atherosclerosis. Endothelial cells produce superoxide anions (O2.-) and oxidize LDL in vitro; however, the role of O2.- in endothelial cell-induced LDL oxidation is unclear. Incubation of human LDL (200 microg/mL) with bovine aortic endothelial cells (BAECs) for 18 hours resulted in a 4-fold increase in LDL oxidation compared with cell-free incubation (22.5+/-1.1 versus 6.3+/-0.2 [mean+/-SEM] nmol malondialdehyde/mg LDL protein, respectively; P<0.05). Under similar conditions, incubation of LDL with porcine aortic endothelial cells resulted in a 5-fold increase in LDL oxidation. Inclusion of exogenous copper/zinc superoxide dismutase (Cu/ZnSOD, 100 microg/mL) in the medium reduced BAEC-induced LDL oxidation by 79%. To determine whether the intracellular SOD content can have a similar protective effect, BAECs were infected with adenoviral vectors containing cDNA for human Cu/ZnSOD (AdCu/ZnSOD) or manganese SOD (AdMnSOD). Adenoviral infection increased the content and activity of either Cu/ZnSOD or MnSOD in the cells and reduced cellular O2.- release by two thirds. When cells infected with AdCu/ZnSOD or AdMnSOD were incubated with LDL, formation of malondialdehyde was decreased by 77% and 32%, respectively. Two other indices of LDL oxidation, formation of conjugated dienes and increased LDL electrophoretic mobility, were similarly reduced by SOD transduction. These data suggest that production of O2.- contributes to endothelial cell-induced oxidation of LDL in vitro. Furthermore, adenovirus-mediated transfer of cDNA for human SOD, particularly Cu/ZnSOD, effectively reduces oxidation of LDL by endothelial cells.
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PMID:Overexpression of human superoxide dismutase inhibits oxidation of low-density lipoprotein by endothelial cells. 964 25

Our group recently observed that manganese prevents oxidative brain injury in the iron-induced parkinsonian animal model. It has also been suggested that manganese retards while copper promotes the development of atherosclerosis. In this report, we provide further evidence to support a controversial notion that manganese is an atypical antioxidant. Among transition metals, Cu2+ and Fe2+ (0.1 to 125 microM), but not Mn2+, converted hydrogen peroxide to reactive hydroxyl radicals via the Fenton reaction at pH 7.4. Iron's pro-oxidative rate is relatively slow, but it is accelerated further by ascorbate (50 microM) in 37 degrees C Dulbecco's phosphate buffered saline. Moreover, Mn2+ (0-80 microM) concentration dependently retarded diene conjugation of human low density lipoproteins stimulated by 5 microM Cu2+. This new result is consistent with our recent finding that Mn2+ (0 to 20 microM) does not initiate brain lipid peroxidation while it inhibits iron-induced peroxidation of polyunsaturated fatty acids. These unexpected manganese results are somewhat at odds with a prominent theory that manganese is a prooxidative transition metal. Furthermore, iron and copper induced free radical generation and lipid peroxidation are suppressed by lowering the incubation temperature; this suggests that hypothermia may decrease the oxidative stress and damage in vivo. In conclusion, normal dietary intake of manganese may protect cells and neurons from oxidant stress through the inhibition of propagation of lipid peroxidation caused by hydroxyl radicals generated by pro-oxidative transition metals such as iron and copper. Potential therapeutical uses of manganese, manganese SOD mimetics and hypothermia for protecting brain neurons and vascular endothelial cells against oxidative stress and damage have been successfully demonstrated in both animal models and clinical trials.
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PMID:Implications for atypical antioxidative properties of manganese in iron-induced brain lipid peroxidation and copper-dependent low density lipoprotein conjugation. 1038 4

Changes were studied in the blood plasma content of trace elements (iron, zinc, manganese, copper and zinc) before and after a 20-day course of treatment in patients with IHD, stable angina, who were given, apart from antianginal therapy, eunicap M having in its composition trace elements (iron, manganese, cuprum, and other trace elements). It has been ascertained that IHD is accompanied by changes in the blood plasma content of trace elements. Combination of eunicap M with antianginal therapy promotes the tendency toward normalization of iron and cuprum metabolism; there was no significant change in the content of zinc and manganese, which fact may be related to a deficient content of manganese in the given drug preparation or a greater demand for them in patients with atherosclerosis.
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PMID:[The correction of the trace element composition of the blood plasma in patients with ischemic heart disease by using Eunicap M]. 1042 18

Endothelium-dependent relaxations mediated by NO are impaired in a mouse model of human atherosclerosis. Our objective was to characterize the mechanisms underlying endothelial dysfunction in aortas of apolipoprotein E (apoE)-deficient mice, treated for 26 to 29 weeks with a lipid-rich Western-type diet. Aortic rings from apoE-deficient mice showed impaired endothelium-dependent relaxations to acetylcholine (10(-)(9) to 10(-)(5) mol/L) and Ca(2+) ionophore (10(-)(9) to 10(-)(6) mol/L) and endothelium-independent relaxations to diethylammonium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA-NONOate, 10(-)(10) to 10(-)(5) mol/L) compared with aortic rings from C57BL/6J mice (P<0.05). By use of confocal microscopy of an oxidative fluorescent probe (dihydroethidium), increased superoxide anion (O(2)(-)) production was demonstrated throughout the aortic wall but mainly in smooth muscle cells of apoE-deficient mice. CuZn-superoxide dismutase (SOD) and Mn-SOD protein expressions were unaltered in the aorta exposed to hypercholesterolemia. A cell-permeable SOD mimetic, Mn(III) tetra(4-benzoic acid) porphyrin chloride (10(-)(5) mol/L), reduced O(2)(-) production and partially normalized relaxations to acetylcholine and DEA-NONOate in apoE-deficient mice (P<0.05). [(14)C]L-Citrulline assay showed a decrease of Ca(2+)-dependent NOS activity in aortas from apoE-deficient mice compared with C57BL/6J mice (P<0.05), whereas NO synthase protein expression was unchanged. In addition, cGMP levels were significantly reduced in the aortas of apoE-deficient mice (P<0.05). Our results demonstrate that in apoE-deficient mice on a Western-type fat diet, impairment of endothelial function is caused by increased production of O(2)(-) and reduced endothelial NO synthase enzyme activity. Thus, chemical inactivation of NO with O(2)(-) and reduced biosynthesis of NO are key mechanisms responsible for endothelial dysfunction in aortas of atherosclerotic apoE-deficient mice.
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PMID:Mechanism of endothelial dysfunction in apolipoprotein E-deficient mice. 1139 13

This review describe the effect of manganese on the heart and blood vessels. The interaction between manganese and redox systems and manganese contribution to atherosclerosis development were also investigated. The results of the experimental studies on animals, on isolated blood vessels in vitro and on people professionally exposed to manganese were presented.
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PMID:[Effect on manganese on the circulatory system]. 1258 29

Oxidative stress plays a pivotal role in the pathogenesis of atherosclerosis and can be effectively influenced by radical scavenging enzyme activity and expression. The vasoprotective effects of estrogens may be related to antioxidative properties. Therefore, effects of 17beta-estradiol on production of reactive oxygen species and radical scavenging enzymes were investigated. 17beta-estradiol diminished angiotensin II-induced free radical production in vascular smooth muscle cells (DCF fluorescence laser microscopy). 17beta-estradiol time- and concentration-dependently upregulated manganese (MnSOD) and extracellular superoxide dismutase (ecSOD) expression (Northern and Western blotting) and enzyme activity (photometric assay). Nuclear run-on assays demonstrated that 17beta-estradiol increases MnSOD and ecSOD transcription rate. Half-life of MnSOD mRNA was not influenced, whereas ecSOD mRNA was stabilized by estrogen. Copper-zinc SOD, glutathione-peroxidase, and catalase were not affected by estrogen. Estrogen deficiency in ovariectomized mice induced a downregulation of ecSOD and MnSOD expression, which was associated with increased production of vascular free radicals and prevented by estrogen replacement or treatment with PEG-SOD. In humans, increased estrogen levels led to enhanced ecSOD and MnSOD expression in circulating monocytes. Estrogen acts antioxidative at least to some extent via stimulation of MnSOD and ecSOD expression and activity, which may contribute to its vasoprotective effects.
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PMID:Modulation of antioxidant enzyme expression and function by estrogen. 1281 84


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