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

Cultured smooth muscle cells from pig aortas were incubated with low density lipoproteins (LDL) and chloroquine for up to 5 days, as an in vitro model for lipid accumulation in atherosclerosis. Cells incubated with LDL alone had a normal morphology, except that some cells contained large lipid droplets. The activities of acid phosphatase, catalase and malate dehydrogenase were increased in homogenates prepared from these cells. Cells incubated with chloroquine alone developed large autophagic vacuoles. The activities of the three acid hydrolases, acid phosphatase, N-acetyl-beta-glucosaminidase and beta-glucuronidase, were decreased, as was the proteolytic activity of the cell homogenates at acid pH toward 125I-labelled LDL. There was, however, a transient increase in the activity of malate dehydrogenase. Chloroquine by itself was toxic to the cells, but LDL protected against this toxic effect. Cells incubated with LDL and chloroquine together developed both autophagic vacuoles and large lipid droplets. The cholesteryl ester content of the cells was increased many-fold and the non-esterified cholesterol content was increased to a lesser extent. The above four acid hydrolase activities were decreased, as was the activity of catalase, whereas the activities of lactate dehydrogenase and malate dehydrogenase were increased.
Atherosclerosis 1982 Sep
PMID:Lipid accumulation in arterial smooth muscle cells in culture. Morphological and biochemical changes caused by low density lipoproteins and chloroquine. 715 Mar 93

Male and female, Sprague-Dawley rats, with and without arteriosclerosis, were subjected to chronic treatment with furosemide for 4 weeks. Furosemide-treated rats manifested increased adrenal and kidney weights along with an increase in blood pressure; rats with pre-existing arteriosclerosis showed considerable reduction in heart and body weights. Furosemide-treated animals displayed an increase in circulating levels of creatine phosphokinase, lactic dehydrogenase, free fatty acids, glucose, BUN and uric acid. Circulating levels of triglycerides, total cholesterol, and corticosterone were subnormal, whereas aldosterone was distinctly elevated. Despite these metabolic derangements, de novo arterial disease did not appear in virgin rats without pre-existing arterial disease. However, furosemide-treated virgin rats did develop grossly visible apical and left-ventricular foci of myocardial necrosis, i.e., 12% in males, 9% in female virgins. Breeder rats with pre-existing arteriosclerosis manifested exacerbation of their arterial disease, e.g., intimal calcification of the epicardial coronary arteries along with foci of myocardial fibrosis and islet beta-cell granule depletion. Adrenocortical lipid alterations appeared in all animals treated with furosemide. It is suggested that this spectrum of metabolic and histopathologic degenerative changes may have been caused by secondary aldosteronism due to the chronic treatment with furosemide.
Atherosclerosis 1981 May
PMID:Furosemide-induced hyperuricemia, hyperglycemia, hypertension and arterial lesions in nonarteriosclerotic and arteriosclerotic rats. 724 2

Study of the key mechanisms, metabolism regulators, showed that in the blood of patients with atherosclerosis the NAD/NAD . N ratio decreases by 59.8% and the NAD+ concentration by 44%, while the NAD . N content increases by 56.7%. In the nicotinamide adenine dinucleotide system there is a general tendency tomards accumulation:the concentration of NADP+ grows by 218.6% and that of NADP . N by 12.9%. A marked increase in the content of incompletely oxidized products is determined: lactic acid by 37.4%, alpha-glycerophosphate by 49.8%, dihydroxyacetone phosphate by 155%, oxaloacetate by 131% in the presence of lactate dehydrogenase and malate dehydrogenase activation. The detected changes are evidence of tissue energy debt in atherosclerosis, they reflect the character of metabolic acidosis formation and point to the presence of conditions for intensified liposynthesis.
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PMID:[Content of nicotinamide coenzymes, metabolites and the NAD-dependent dehydrogenase activity in the blood in arteriosclerosis]. 737 12

The effects of lysophosphatidylcholine (LPC), a vasoactive phospholipid, on intracellular free calcium concentration ([Ca2+]i), DNA synthesis and cytotoxicity of vascular smooth muscle cells (VSMC) were studied. LPC from 10(-7) to 10(-5) mol/l dose-dependently induced a sustained increase in [Ca2+]i. In contrast to the response of [Ca2+]i induced by angiotensin II, that induced by LPC was totally abolished when extracellular Ca2+ was removed, was not affected by pretreatment of the cells with islet-activating protein, and was not desensitized by repeated addition. 8-(N,N-Diethylamino)octyl 3,4,5-trimethoxybenzoic acid (TMB-8), an inhibitor of Ca2+ release from intracellular Ca2+ stores, 1-(5-isoquinolinesulfonyl)-2-methylpiperadine dihydrochloride (H-7), an inhibitor of protein kinase C, KT5823, an inhibitor of protein kinase G, and Ca2+ channel blockers failed to suppress the LPC-induced increase in [Ca2+]i. LPC at 10(-5) mol/l caused significant stimulation of [3H]thymidine incorporation into VSMC, and at concentrations of 10(-5) mol/l and higher dose-dependently stimulated release of lactate dehydrogenase in cell culture supernatants. Moreover, digitonin mimicked the effects of LPC on [Ca2+]i, and also caused similar effects to those of LPC on DNA synthesis and cytotoxicity in VSMC. These observations suggest that LPC causes both cell growth and cell injury of VSMC, at least partly, through its detergent action, causing membrane leakiness and resultant [Ca2+]i overload in vitro, thus indicating the possible participation of LPC in atherosclerosis and/or injury of the vascular wall.
Atherosclerosis 1995 Jan 06
PMID:Lysophosphatidylcholine causes Ca2+ influx, enhanced DNA synthesis and cytotoxicity in cultured vascular smooth muscle cells. 777 68

The action of gypenosides (GP, saponins of Gynostemma pentaphyllum, a Chinese medicinal herb) as an antioxidant was studied using various models of oxidant stress in phagocytes, liver microsomes and vascular endothelial cells. The results show that GP decreased superoxide anion and hydrogen peroxide content in human neutrophils and diminished chemiluminescent oxidative burst triggered by zymosan in human monocytes and murine macrophages. An increase of lipid peroxidation induced by Fe2+/cysteine, ascorbate/NADPH or hydrogen peroxide in liver microsomes and vascular endothelial cells was inhibited by GP. It was also found that GP protected biomembranes from oxidative injury by reversing the decreased membrane fluidity of liver microsomes and mitochondria, increasing mitochondrial enzyme activity in vascular endothelial cells and decreasing intracellular lactate dehydrogenase leakage from these cells. The extensive antioxidant effect of GP may be valuable to the prevention and treatment of various diseases such as atherosclerosis, liver disease and inflammation.
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PMID:Protective effect of gypenosides against oxidative stress in phagocytes, vascular endothelial cells and liver microsomes. 780 67

The present study demonstrates for the first time that iron ions can induce lipid peroxidation in intact macrophages without causing cell death. Macrophage lipid peroxidation increases cell-mediated oxidation of LDL, enhances the release of interleukin 1 and inhibits the release of apolipoprotein E from the macrophages. When cultured macrophages were exposed to ferrous ions (50 microM FeSO4) for 4 h at 37 degrees C, cellular lipid peroxidation (measured by analyses of malondialdehyde (MDA), conjugated dienes (CD), and lipid peroxides (PD)) increased 2-4-fold in comparison with non-treated cells. This process was iron-dose dependent, reached its maximum after 4 h of incubation, and was accompanied by 68% and 53% reductions in the content of the cellular linoleic (18:2), and arachidonic acid (20:4), respectively, and by 29% and 36% reductions of cellular vitamin E and vitamin A, respectively. Cell viability (measured by trypan blue exclusion, by [3H]thymidine incorporation into DNA, by analysis of the release of lactate dehydrogenase (LDH) or [3H]adenine), and cell morphology (studied by scanning electron microscopy) were not significantly affected by the iron-induced oxidative stress. Manitol and dimethylthiourea (DMTU), but not catalase or superoxide dismutase (SOD), significantly inhibited iron-induced cellular lipid peroxide formation, suggesting that hydroxyl radical, but not superoxides or hydrogen peroxides, mediated the iron-induced cellular lipid peroxidation. Incubation of LDL (0.2 mg of protein/ml) with oxidized macrophages resulted in LDL lipids peroxidation, as evidenced by an 8-fold increase in the LDL associated MDA in comparison with LDL that was incubated under similar conditions with non-oxidized macrophages. Furthermore, oxidation of LDL by oxidized macrophages in the presence of copper ions (10 microM CuSO4) was 2-fold higher in comparison with oxidation of LDL by non-oxidized macrophages. The release of apolipoprotein E from oxidized macrophages decreased by 50%, whereas macrophage release of beta-glucuronidase and of interleukin-1 beta increased by 83% and by a factor of 6, respectively. This study demonstrates for the first time that iron ions induce oxidation of the cellular polyunsaturated fatty acids in intact macrophages and that this cellular lipid peroxidation can subsequently induce LDL oxidation.
Atherosclerosis 1994 Nov
PMID:Iron induces lipid peroxidation in cultured macrophages, increases their ability to oxidatively modify LDL, and affects their secretory properties. 784 Aug 15

Low density lipoprotein (LDL) deposition and local oxidation play a key role in the pathogenesis of atherosclerosis and may likewise contribute to glomerular injury. These studies were designed to determine whether cultured human mesangial cells oxidize homologous LDL and to compare the effects of unmodified and oxidized lipoprotein on cell proliferation, viability and eicosanoid production. Cell-mediated lipoprotein oxidation was demonstrated and could be suppressed by oxygen free radical scavengers and inhibitors of arachidonic acid metabolism. When incubated with cells, oxidized LDL (Ox-LDL) at concentrations up to and including 100 micrograms/ml reduced 3H-thymidine incorporation without causing cytotoxicity as assessed by lactate dehydrogenase release. Under the same conditions there was a concentration-dependent increase in the synthesis of prostaglandins E2,6-keto-PGF1 alpha and thromboxane B2. In contrast, unmodified LDL enhanced DNA synthesis at concentrations less than 40 micrograms/ml and had little effect on eicosanoid production. These results demonstrate that exogenous oxidized LDL inhibits mesangial cell proliferation and increases eicosanoid synthesis. Unmodified lipoprotein can be directly oxidized by these cells through mechanisms that involve generation of oxygen free radicals.
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PMID:Oxidation of low density lipoprotein by mesangial cells may promote glomerular injury. 793 10

Oxidative modification of low-density lipoprotein (LDL) may play an important role in the initiation and progression of atherosclerosis. We previously showed that the cytotoxicity of oxidized LDL (oxLDL) depended on the level of lipid hydroperoxides. Meanwhile, it has been shown that during LDL oxidation, a significant part of the LDL phosphatidylcholine (PC) is degraded to lysophosphatidylcholine (LPC) by an intrinsic phospholipase A2-like activity, and that LPC is toxic to various cells. In the present study, we compared the toxicity of oxLDL with that of LPC in cultured bovine aortic endothelial cells. Cytotoxicity induced by LPC, assessed by the release of lactate dehydrogenase (LDH), reached a plateau within 1 h. LDH release induced by oxLDL occurred much later, at about 3 h, and increased linearly until nearly all the LDH was released at 10 h. The addition of deferoxamine, a Fe3+ chelator, to the reaction medium prevented the toxic effects of oxLDL, but not of LPC. Native LDL and oxLDL inhibited the toxicity of LPC, while native LDL promoted the toxicity of oxLDL. Albumin inhibited the toxicity of LPC but not of oxLDL. Preincubation of endothelial cells with an antioxidant, probucol, protected against oxLDL toxicity, but not against LPC toxicity. These results suggest that lipid hydroperoxides associated with the oxLDL particle, not LPC, constitute the toxic moiety of oxLDL. These substances may generate lipid peroxyl and alkoxyl radicals in the presence of ionic iron, probably from intracellular iron stores in endothelial cells, and produce cytotoxicity.
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PMID:Comparative toxicity of oxidatively modified low-density lipoprotein and lysophosphatidylcholine in cultured vascular endothelial cells. 796 Dec 95

Alteration of glycosaminoglycans (GAGs) in cultured bovine aortic smooth muscle cells after exposure to cadmium was investigated. It was revealed that cadmium increased the accumulation of GAGs metabolically labeled with [3H]glucosamine but decreased that with [35S]sulfate in the cell fraction, the cell surface fraction and the medium fraction. This suggested that cadmium stimulated the biosynthesis of GAGs but inhibited their sulfation in the cells. A similar alteration was observed in cadmium-treated human aortic smooth muscle cell layer. Of tested cations including cadmium, bismuth, cobalt, copper, lead, manganese, nickel and zinc, only cadmium stimulated [3H]glucosamine incorporation, with a strong inhibition of the [35S]sulfate incorporation in the bovine cells. Characterization of bovine smooth muscle GAGs showed that the cadmium-induced increase in the [3H]glucosamine incorporation was mainly observed in heparan sulfate; the inhibition of the [35S]sulfate incorporation occurred non-selectively. Cadmium accumulated in bovine vascular smooth muscle cells in a dose-dependent manner with an increase in the leakage of lactate dehydrogenase into the medium. The present data suggest that vascular smooth muscle cells respond to the cytotoxicity of cadmium and promote the GAG synthesis with a reduction of their sulfation. It is postulated that this response may be a defensive one to the damage of the vascular tissue caused by cadmium but would be a component of the metal-induced atherosclerosis.
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PMID:Alteration of glycosaminoglycans induced by cadmium in cultured vascular smooth muscle cells. 799 22

Oxidant injury of the vascular endothelium is considered an early event in the pathogenesis of atherosclerosis. The model of oxidant injury is crucial to the investigation of antioxidants. In the present study, a convenient in vitro model of oxidant injury induced by hydrogen peroxide (H2O2) was developed using bovine pulmonary artery endothelial cells (PAEC). Viability of PAEC grown in 96-well culture plates was determined with methylthiazol tetrazolium (MTT) colorimetric assay. Cell membrane integrity was measured by lactate dehydrogenase (LDH) release from PAEC grown in 24-well plates. Malondialdehyde (MDA, a product of lipid peroxidation) in PAEC grown in 6-well plates was detected by a thiobarbituric acid fluorometric assay. Incubation of H2O2 with PAEC caused a dose-dependent decrease of cell viability, an increase of LDH release, and an elevation of MDA production. MTT assay was convenient, quantitative, non-radioactive, and suitable for testing a large number of samples. The fluorometric assay for measuring MDA production in endothelial cells used 6-well plates instead of 80-cm2 flasks employed by previous investigators. The use of multiwell culture plates in these assays made it possible for more samples to be tested in any single experiment. The three assays are reproducible with low intraplate and interplate coefficients of variation. This in vitro model is suitable for screening antioxidants and for studying pharmacodynamics at the cellular level.
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PMID:A simplified in vitro model of oxidant injury using vascular endothelial cells. 835 64


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