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

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

Oxidant injury of the vascular endothelium is considered an early event in the pathogenesis of atherosclerosis. In this study, the antioxidant effect of a 6-kDa thymic peptide (TP), isolated from calf thymus, was investigated in vitro using vascular endothelial cells. Confluent monolayers of bovine pulmonary artery endothelial cells (PAEC) were preincubated with different concentrations of TP for 24 h, washed, and then exposed to hydrogen peroxide (H2O2) for 2 or 4 h. Cell injury was assessed by measuring cell viability with methylthiazol tetrazolium (MTT) assay, and by determining the release of intracellular lactate dehydrogenase (LDH). Lipid peroxidation products of PAEC were monitored as malondialdehyde (MDA) with a thiobarbituric acid fluorometric assay. H2O2 (120 or 240 microM) incubated with PAEC decreased cell viability, increased LDH release, and elevated MDA production. Preincubation of PAEC with TP (25-150 micrograms/ml) before H2O2 exposure significantly increased cell viability, decreased LDH release, and reduced MDA production. These results demonstrate that TP can protect vascular endothelial cells from oxidant injury. The data thus suggest that TP may be useful for the prevention and/or treatment of atherosclerosis, and further suggest that immune modulating agents may directly or indirectly influence the functions of vascular endothelium.
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PMID:Thymic peptide protects vascular endothelial cells from hydrogen peroxide-induced oxidant injury. 849 41

The active oxygen induced and free radical mediated oxidation of biological molecules, membranes, and tissues has been suggested as a major cause of cancer, atherosclerosis, and aging. Damage of endothelial cells may lead to cardiovascular and cerebrovascular diseases. In the present study, the antioxidant effect of pycnogenol (procyanidins extracted from Pinus maritima) was investigated in vitro using vascular endothelial cells. Confluent monolayers of bovine pulmonary artery endothelial cells (PAEC) were preincubated with different concentrations of pycnogenol for 16 h, washed, and then exposed to an organic oxidant t-butyl hydroperoxide (tBHP) for 3 or 4 h. Cellular injury was assessed by measuring cell viability with methylthiazol tetrazolium (MTT) assay and by determining the release of intracellular lactate dehydrogenase (LDH). Lipid peroxidation products of PAEC were monitored as malondialdehyde (MDA) with a thiobarbituric acid fluorometric assay. Incubation of tBHP (75, 100, or 125 microM) with PAEC decreased cell viability, increased LDH release, and elevated MDH production. Preincubation of PAEC with pycnogenol (10-80 micrograms/mL) before tBHP exposure significantly increased cell viability, decreased LDH release, and reduced MDA production. These results demonstrate that pycnogenol can protect vascular endothelial cells from oxidant injury. The data thus suggest that pycnogenol may be useful for the prevention of disorders associated with oxidative damage.
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PMID:Pycnogenol protects vascular endothelial cells from t-butyl hydroperoxide induced oxidant injury. 860 22

The preventative effects of bifemelane (4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride) on atherosclerosis in aged rats fed low-calcium diets were investigated. Male 18-month-old Wistar rats were maintained for 90 days on the following: (A) standard diet (n = 7), (B) low calcium, low magnesium, high aluminium diet (n = 8), (C) standard diet plus oral intubation with 10 mg bifemelane/kg daily (n = 6), (D) low calcium and magnesium, high aluminium diet plus oral intubation with 10 mg bifemelane/kg daily (n = 6). All groups were give these diets and water ad lib for 90 days, after which blood samples were taken from the abdominal aorta and samples of aorta were examined for atherosclerotic changes. The serum concentrations of the following were determined: calcium, magnesium, zinc, aluminium, inorganic phosphorus, cholesterol, glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase, lactate dehydrogenase, cholinesterase, creatine phosphokinase, blood urea nitrogen and N-terminal parathyroid hormone. The only significant differences between the groups in serum chemistry were reduced concentrations of cholinesterase and magnesium in groups B and D, increased aluminium in group B, and increased N-terminal parathyroid hormone in groups B and D. In groups C and D the atherosclerosis was much improved compared with that in groups A and B. It appears that bifemelane largely prevents atherosclerosis caused by calcium deposition in the arteries of rats fed low-calcium diets, due to its effect in maintaining magnesium and calcium in bones.
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PMID:Effects of bifemelane hydrochloride on atherosclerosis in aged rats fed low-calcium diets. 895 29

The aim of this study was to examine the effects of the water soluble component of cigarette smoke extract (CSE) on endothelium-dependent relaxation (EDR) of isolated rabbit aortas. The incubation with CSE was found to inhibit EDR in a dose-dependent manner. Co-incubation of the aortic strips with superoxide dismutase (SOD), N-acetylcysteine, glutathione or dimethyl sulfoxide (DMSO), free radical scavengers, attenuated the CSE-induced inhibition of the arterial relaxation. Co-incubation of the strips with captopril (3 mM), an angiotensin converting enzyme inhibitor, also attenuated CSE-induced impairment of vasorelaxation. In parallel experiments using cultured human endothelial cells, CSE suppressed endothelial release of NOx, stable metabolites of nitric oxide (NO). SOD, DMSO and captopril attenuated the suppression of NO production by CSE in association with reduction of free radicals, superoxide anions and hydroxyl radicals, in CSE solution. Neither lactate dehydrogenase release from the cultured endothelial cells nor cell death estimated by trypan blue exclusion test was found after the incubation of the cultured endothelial cells with CSE. The results indicate that free radicals in CSE induce the impairment of EDR, which may be partly due to suppression of NO production and is not due to non-specific cytotoxicity by CSE. Captopril attenuates CSE-induced endothelial dysfunction partly through scavenging free radicals.
Atherosclerosis 1997 Jun
PMID:Impairment of endothelium-dependent relaxation of rabbit aortas by cigarette smoke extract--role of free radicals and attenuation by captopril. 919 72


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