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 goal of the present study was to determine whether oxygen-derived free radicals contribute to baroreceptor dysfunction in atherosclerosis. Baroreceptor activity was measured from the carotid sinus nerve during pressure ramps in isolated carotid sinuses of anesthetized rabbits. Rabbits fed a 0.5% to 1.0% cholesterol diet for 7.9 +/- 0.4 months (mean +/- SE; range, 5.5 to 10) developed atherosclerotic lesions in the carotid sinuses. Maximum baroreceptor activity measured at 140 mm Hg and the slope of the pressure-activity curve were reduced in atherosclerotic (n = 15) compared with normal (n = 13) rabbits (425 +/- 34 versus 721 +/- 30 spikes per second and 6.2 +/- 0.6 versus 10.8 +/- 0.8 spikes per second per mm Hg, respectively, P < .05). The level of activity was inversely related to plasma cholesterol concentration (r = .86, P < .001) and total cholesterol load (plasma concentration x duration of diet, r = .92). Mean arterial pressure was normal in both groups. Exposure of the carotid sinus to the free-radical scavengers superoxide dismutase (SOD) and catalase significantly increased maximum baroreceptor activity by 25 +/- 4% in atherosclerotic rabbits (n = 6) but caused only small and irreversible changes in activity in normal rabbits (n = 8). Catalase alone but not SOD also increased baroreceptor activity in atherosclerotic rabbits (n = 7). Exposure of the carotid sinus of normal rabbits to exogenous free radicals generated from the reaction between xanthine and xanthine oxidase inhibited baroreceptor activity in a dose-dependent and reversible manner (n = 8, P < .05). The inhibition of activity was attenuated by SOD and catalase but was not attenuated by the inhibitor of hydroxyl radical formation, deferoxamine. Neither restoration of baroreceptor activity in atherosclerotic rabbits by catalase nor inhibition of activity by xanthine/xanthine oxidase could be explained by changes in the carotid pressure-diameter relation or prostacyclin formation. These results indicate that oxidant stress inhibits baroreceptor activity and that endogenous oxyradicals produced in atherosclerotic carotid sinuses contribute to baroreceptor dysfunction.
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PMID:Oxygen-derived free radicals contribute to baroreceptor dysfunction in atherosclerotic rabbits. 883 4

Nicotine, a major component of cigarette smoke, plays an important role in the development of cardiovascular disease and lung cancer in smokers. Lipid peroxidation is a process associated with the pathogenesis of atherosclerosis and the level of lipid peroxides is increased in smokers. In rats fed a high-fat diet, the tissue concentration of lipid peroxides was found to be increased. On nicotine administration along with a high-fat diet an additive effect was observed in lipid peroxidation and free radical scavengers. The activities of scavenging enzymes superoxide dismutase, catalase and glutathione reductase were found to be decreased, while the glutathione concentration and activity of glutathione peroxidase were enhanced.
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PMID:Effect of nicotine on antioxidant defence mechanisms in rats fed a high-fat diet. 884 84

Increased generation of active oxygen species such as hydrogen peroxide (H202) may be important in vascular smooth muscle cell growth associated with atherosclerosis and restenosis. In this work, we showed that H202 was a potent mitogen for growth-arrested cultured human aortic smooth muscle cells (SMC), stimulating an increase in cell number at 10 nM to 100 microM concentration. This effect was inhibited in a dose-dependent manner by catalase, deferoxamine, dimethylthiourea or probucol showing that it was dependent on the oxidative activity of H202. H202-induced SMC proliferation was strongly and specifically inhibited by a neutralizing monoclonal antibody directed against basic fibroblast growth factor (bFGF) but was not due to increased expression of bFGF or the bFGF receptor-1 (FGFR-1) by SMC. H202 strongly increased the affinity of bFGF for its receptor-1 at the surface of the SMC, therefore showing that the mitogenic effect of H202 might occur through a direct effect on the bFGF receptor.
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PMID:The mitogenic effect of H2O2 for vascular smooth muscle cells is mediated by an increase of the affinity of basic fibroblast growth factor for its receptor. 884 86

Cigarette smoking has been established as a major risk factor for atherosclerosis and also for lung cancer. Nicotine is one of the major toxic components of cigarette smoke that is believed to be partly responsible for the deleterious effect of cigarette smoke. Alcohol intake is another major risk factor for the development of cardiovascular disease. Lipid peroxidation is a process associated with the pathogenesis of atherosclerosis. The concentration of lipid peroxides is found to be increased in alcohol-treated rats. On nicotine administration along with alcohol, an additive effect was observed in lipid peroxidation and the antioxidant defence mechanism. The activity of scavenging enzymes superoxide dismutase, catalase and glutathione reductase was found to be decreased, while the activity of glutathione peroxidase and the concentration of glutathione were increased.
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PMID:Additive effect of alcohol and nicotine on lipid peroxidation and antioxidant defence mechanism in rats. 885 16

N(epsilon)-(Carboxymethyl)lysine (CML), a major product of oxidative modification of glycated proteins, has been suggested to represent a general marker of oxidative stress and long-term damage to proteins in aging, atherosclerosis, and diabetes. To investigate the occurrence and distribution of CML in humans an antiserum specifically recognizing protein-bound CML was generated. The oxidative formation of CML from glycated proteins was reduced by lipoic acid, aminoguanidine, superoxide dismutase, catalase, and particularly vitamin E and desferrioxamine. Immunolocalization of CML in skin, lung, heart, kidney, intestine, intervertebral discs, and particularly in arteries provided evidence for an age-dependent increase in CML accumulation in distinct locations, and acceleration of this process in diabetes. Intense staining of the arterial wall and particularly the elastic membrane was found. High levels of CML modification were observed within atherosclerotic plaques and in foam cells. The preferential location of CML immunoreactivity in lesions may indicate the contribution of glycoxidation to the processes occurring in diabetes and aging. Additionally, we found increased CML content in serum proteins in diabetic patients. The strong dependence of CML formation on oxidative conditions together with the increased occurrence of CML in diabetic serum and tissue proteins suggest a role for CML as endogenous biomarker for oxidative damage.
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PMID:Increased accumulation of the glycoxidation product N(epsilon)-(carboxymethyl)lysine in human tissues in diabetes and aging. 902 79

Heme-containing (per)oxidases including horse radish peroxidase (HRP)/H2O2 have been shown to oxidatively modify isolated low-density lipoprotein (LDL) in vitro and oxidized LDL is implicated in the early events leading to atherosclerosis. The role of alpha-tocopherol (alpha-TOH) in the oxidation of LDL by HRP/H2O2 is unclear, although alpha-tocopheroxyl radical (alpha-TO.), which is formed during this process, can act as a chain transfer agent of lipid peroxidation in LDL. By combining HPLC and EPR spectroscopy, we hereby show that during HRP/H2O2-induced oxidation of human LDL: (i) the accumulation of cholesteryl linoleate hydroperoxides and hydroxides (CE-O(O)H) occurs concomitantly with the formation of alpha-TO. and consumption of alpha-TOH in the absence of other detectable organic (g approximately 2) radicals; (ii) the rates of alpha-TO. formation and subsequent decay reflect the rates of both alpha-TOH consumption and CE-O(O)H accumulation; (iii) CE-O(O)H accumulation is directly dependent on the level of endogenous alpha-TOH, and vitamin E supplementation results in increased lipid oxidizability; (iv) the inhibition of HRP activity by catalase plus urate results in a persistent alpha-TO. signal, the decay (t1/2 approximately 20 min) of which is accompanied by continued accumulation of CE-O(O)H, with complete cessation of lipid peroxidation upon loss of the chromanoxyl signal. These results demonstrate a direct correlation between alpha-TOH/alpha-TO. and the extent of HRP/H2O2-induced LDL lipid peroxidation, and that this type of oxidative modification can occur in the absence of g approximately 2 radicals other than alpha-TO.. Together, the results support a role for tocopherol-mediated peroxidation but not the involvement of a protein radical in the initiation of LDL lipid peroxidation induced by HRP/H2O2.
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PMID:Role of alpha-tocopheroxyl radical in the initiation of lipid peroxidation in human low-density lipoprotein exposed to horse radish peroxidase. 906 73

Reactive oxygen species (ROS) are cytotoxic, causing inflammatory disease, including tissue necrosis, organ failure, atherosclerosis, infertility, birth defects, premature aging, mutations and malignancy. ROS are produced in the metabolism of drugs and industrial chemicals by (i) one-electron peroxidase oxidations to form cation radicals, (ii) cytochrome P450 metabolism to free radical products, (iii) stabilisation of the ROS-generator, CYP2E1, and (iv) futile cycling of other cytochromes P450. ROS production initiates inflammation which unless quenched may result in chronic inflammatory disease states, e.g. hepatitis, nephritis, myositis, scleroderma, lupus erythematosus, multiple system organ failure. Quenching of ROS is affected by the redox buffer, glutathione (GSH), and the antioxidants, ascorbic acid, tocopherols, retinoids, in conjunction with the redox enzymes, GSH reductase, GSH peroxidase, catalase and superoxide dismutase. Many industrial workers with symptoms of systemic inflammation, resulting from exposure to toxic chemicals, are diagnosed as having rheumatoid arthritis, virus infections, or other microbial lesions, largely because many physicians are unaware that exposure to certain chemicals can initiate inflammatory disease states.
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PMID:Chemical toxicity and reactive oxygen species. 911 92

Apoptosis of vascular smooth muscle cell (VSMC) plays an important role in the genesis of atherosclerosis and restenosis. In order to investigate the role of reactive oxygen species in the induction of VSMC apoptosis, rat VSMCs were treated with glucose oxidase/glucose (GO/G) or diethylmaleate (DEM). The results showed that GO/G and DEM led to VSMC death. Administration of catalase, superoxide dismutase and deferoxamine revealed that H2O2 was the major reactive oxygen species causing cell death, and H2O2O exerted its effect by formation of hydroxyl radical (.OH). GO/G- and DEM-induced VSMC death occurred by apoptosis characterized by "DNA ladders", condensation of nuclei, positive to in situ nick-end labeling and increases in histone-associated DNA fragmentation. This study suggests that H2O2 and its derived form .OH might be related to apoptosis of VSMC in atherosclerosis and restenosis.
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PMID:Reactive oxygen species induce apoptosis of vascular smooth muscle cell. 911 73

Basic fibroblast growth factor (bFGF) is a mitogenic factor that is implicated in smooth muscle cell growth in atherosclerosis and vascular restenosis. In this study, we examined the effect of bFGF on the expression of the interstitial collagenase gene in human vascular smooth muscle cells. Results from Northern transfer analysis showed that bFGF increased collagenase mRNA levels greater than threefold as early as 24 h. Collagenase pre-mRNA levels were elevated approximately threefold by bFGF, according to RT-PCR analysis. Transient transfections of the smooth muscle cells with a 4.4-kb human collagenase promoter-CAT reporter gene, however, failed to show upregulation of the promoter activity by bFGF. Interestingly, transfections with deleted fragments containing promoter sequences from -1047 to -2271 resulted in modest stimulation of the collagenase-CAT promoter activity by bFGF, bFGF did not alter the stability of the collagenase mRNA, as demonstrated by degradation studies. The enhanced collagenase mRNA levels elicited by bFGF were reflected in increased amounts of collagenase protein that were detected by Western blot analysis. In summary, bFGF upregulates the interstitial collagenase expression, resulting in turnover of the extracellular matrix, an event that could facilitate smooth muscle cell migration and proliferation during the early stages of atherosclerosis and restenosis.
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PMID:Basic FGF regulates interstitial collagenase gene expression in human smooth muscle cells. 913 78

The present study was to investigate the levels of plasma lipid peroxide products including malondialdehyde (MDA) and conjugated dienes (CD), and antioxidants including enzyme superoxide dismutase, glutathione peroxidase, catalase, plasma vitamin E and vitamin C in diabetic patients. Fifty-eight diabetic subjects; 16 males and 42 females, aged 30-75 years, were recruited. Eighteen of them had diabetes and forty of them had diabetes with hyperlipidemia. Twenty-seven healthy subjects, 8 males and 19 females, aged 30-75 years, were used as the control group. The results showed that the concentrations of plasma MDA in diabetic patients with or without hyperlipidemia tended to be increased when compared to the controls but there were no significant differences. The CD values were increased significantly in both diabetic groups when compared with control subjects. Significantly elevated levels of plasma MDA and CD were found in diabetic patients with hypertriglyceridemia (> 150 mg%). This increment did not change the antioxidant status in both enzymes and vitamins except that the plasma vitamin E levels and the ratios of tocopherol: cholesterol were increased significantly. An increase of lipid peroxide in plasma may be one important factor in the development of vascular complication and atherosclerosis seen in diabetic patients.
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PMID:Plasma lipid peroxide and antioxidant levels in diabetic patients. 924 11


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