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)

Heart and red blood cell endogenous antioxidant status and plasma lipids were investigated in hypertensive, 14-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats fed a standard commercial rat chow. Specific heart and red blood cell antioxidant enzyme activities, as well as the susceptibility of tissues to H2O2-induced glutathione (GSH) depletion and lipid peroxidation, were measured. Systolic blood pressure in SHR was greater than in WKY rats at 13 weeks of age (197 +/- 12 vs. 132 +/- 14 mmHg (1 mmHg = 133.3 Pa); p < or = 0.05), confirming the presence of hypertension in SHR. Red blood cell catalase (CAT) and superoxide dismutase (SOD) activities were greater (p < or = 0.05) in SHR than WKY rats. Red blood cell CAT activity was positively correlated (r = +0.634; p = 0.026) with SOD, which in turn was correlated (r = +0.709; p = 0.049) with systolic blood pressure. Heart SOD activity was higher (p < or = 0.05) in SHR, while glutathione reductase (GSSG-Red) activity was lower (p < or = 0.05) than in WKY rats. This reduced ability to recycle GSH in the heart coincided with greater (p < or = 0.05) levels of H2O2-induced lipid oxidation products in SHR. Plasma total cholesterol and triacylglycerol levels were lower (p < or = 0.05) in SHR than WKY rats, with no visible signs of atherosclerosis in either SHR or WKY rats. In summary, hypertension in SHR was associated with alterations in antioxidant enzyme profiles of red blood cells and heart, with the latter showing an increased susceptibility to in vitro lipid oxidation. Although hypertension is a recognized factor in the development of human atherosclerosis, spontaneously hypertensive rats did not exhibit signs of aortic plaque, reflecting the resistance of this species to the development of atherosclerosis.
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PMID:Heart and red blood cell antioxidant status and plasma lipid levels in the spontaneously hypertensive and normotensive Wistar-Kyoto rat. 877 9

Aging of the vascular wall, arteriosclerosis and focal lipidic plaques, atheromatosis, often occur together but may occur separately as lipidic lesions in young children or vascular aging in some animal species resistant to lipid-rich diet as the rat. Most theories of athero-arteriosclerosis claim an endothelial lesion for its initiation, without proposing a detailed mechanism. The elastin-laminin receptor present also on endothelial cells, mediates NO.-dependent vasorelaxation. It could be shown that chronic exposure to higher concentrations of the agonist, elastin peptides, present in human blood at microgram/ml concentrations, and also during aging, the receptor gets "uncoupled" from its transmission pathway (G-protein, PLC, PKC) but continues releasing free radicals as superoxyde. NO. and O2-. give peroxynitrite, a toxic anion, needing GSH for its neutralisation. GSH production decreases with age. This process decreases available NO. for vasorelaxation and could then contribute to age-dependent blood pressure increase and produce the endothelial lesions leading to the development of athero-arteriosclerosis.
Atherosclerosis 1996 Jun
PMID:Aging of the vascular wall and atherogenesis: role of the elastin-laminin receptor. 878 48

The thymus hormones were reported to be effective on lipid peroxidation and the antioxidant system. Thymus plays a broader role than just regulating the immune system. Thymosin alpha 1 is the first subgroup extracted from thymosin F5 and has higher biological activity than thymosin F5. In the present study, we have examined the effects of thymosin alpha 1 on lipid levels and lipid peroxidation and glutathione (GSH) content in the plasma, liver and aorta tissues of atherosclerotic rabbits. At the end of thymosin alpha 1 treatment, we determined the lipid levels and lipid peroxidation of the plasma, liver and aorta tissues and hepatic subcellular fractions in these rabbits. Our results demonstrated that thymosin alpha 1 might normalize changed lipid levels and increased lipid peroxides and also elevate decreased GSH in the plasma, liver and aorta tissues of atherosclerotic rabbits. Results of this study suggest that thymosin alpha 1 may be beneficial to prevent and/or to treat atherosclerosis.
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PMID:Thymosin alpha 1 protects liver and aorta from oxidative damage in atherosclerotic rabbits. 880 25

Considerable progress has been made in the last few years in the molecular identification and characterization of hepatic GSH transporter-associated polypeptides. We are now poised to determine their precise mechanisms of action and regulation at the transcriptional and post-translational level. It is also anticipated that molecular characterization of the mitochondrial GSH transporter and sodium GSH co-transporters will be accomplished in the near future. With this information, a more complete understanding of GSH/cysteine homeostasis can be achieved which can be applied to furthering the prevention and treatment of the diseases of oxidative stress, such as aging, HIV, cataract, atherosclerosis, cancer and alcoholic liver disease.
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PMID:GSH transporters: molecular characterization and role in GSH homeostasis. 882 17

In patients with end-stage renal failure (ESRF), the incidence of atherosclerosis and cancer is increased. The importance of lipid peroxidation (LPO) products in the pathogenesis of these complications has recently been emphasized. The LPO products malondialdehyde (MDA) and hexanal, lipophilic antioxidants and erythrocyte glutathione (GSH) were estimated in 10 pediatric hemodialysis (HD) patients before and after HD and in 11 peritoneal dialysis (CPD) patients. Before HD, MDA was elevated [median (interquartile range): 384.5 (110 to 501) nM; normal < 150 nM], whereas plasma hexanal levels were normal in all patients [130.5 (88 to 222) nM; < 320 nM]. HD decreased MDA concentrations on average by 88% but did not change hexanal levels. CPD patients exhibited high plasma MDA concentrations [371 (287 to 468) nM], whereas hexanal was in the low normal range [56 (51 to 81) nM]. Antioxidants were normal in both groups and unchanged during HD. GSH decreased slightly during HD. We hypothesize that MDA may accumulate in ESRF due to reduced plasma clearance. Our results argue against a general increase of LPO in uremia.
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PMID:Influence of dialysis on plasma lipid peroxidation products and antioxidant levels. 888 87

A profound imbalance between oxidants and antioxidants has been suggested in uremic patients on maintenance hemodialysis. However, the respective influence of uremia and dialysis procedure has not been evaluated. Circulating levels of copper-zinc superoxide dismutase (CuZn SOD), glutathione peroxidase (GSH-Px), and reductase (GSSG-Rd), total GSH and GSSG were determined in a large cohort of 233 uremic patients including 185 undialyzed patients with mild to severe chronic renal failure, and 48 patients treated by peritoneal dialysis or hemodialysis. Compared to controls, erythrocyte GSH-Px and GSSG-Rd activities were significantly increased at the mild stage of chronic uremia (p < .001), whereas erythrocyte CuZn SOD activity was unchanged, total level of GSH and plasma GSH-Px activity were significantly decreased, and GSSG level and GSSG-Rd activity were unchanged. Positive Spearman rank correlations were observed between creatinine clearance and plasma levels of GSH-Px (r = .65, p < .001), selenium (r = .47, p < .001), and GSH (r = .41, p < .001). Alterations in antioxidant systems gradually increased with the degree of renal failure, further rose in patients on peritoneal dialysis and culminated in hemodialysis patients in whom an almost complete abolishment of GSH-Px activity was observed. In conclusion, such disturbances in antioxidant systems that occur from the early stage of chronic uremia and are exacerbated by dialysis provide additional evidence for a resulting oxidative stress that could contribute to the development of accelerated atherosclerosis and other long-term complications in uremic patients.
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PMID:Glutathione antioxidant system as a marker of oxidative stress in chronic renal failure. 890 30

It is now known that human exposure to certain chemicals e.g. benzene, halocarbons, ketones, nitrosamines, etc. can result in adverse health effects that are often not easily recognised as manifestations of chemical toxicity. These are inflammatory states, such as hepatitis, nephritis, scleroderma, and lupus, due to production of reactive oxygen species (ROS) through activation of cytochrome P4502E1 by the chemical, or by metabolism of the chemical to reactive intermediates and neoantigens which initiate immunotoxic effects. Intracellular glutathione (GSH), vitamins C, E and A protect against this ROS toxicity and inflammation; fasting and consumption of alcohol exacerbate it. Chronic inflammatory states may subsequently develop, including rheumatoid disease, atherosclerosis, diabetes, infertility and birth defects, multiple system organ failure (MSOF), Alzheimer's disease, and cancer.
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PMID:Chemical-induced inflammation and inflammatory diseases. 897 63

Malondialdehyde (MDA) is a highly reactive aldehyde generally formed as a consequence of lipid peroxidation. MDA has been inferred to have mutagenic and cytotoxic roles and possibly to be a participant in the onset of atherosclerosis. Wild-type Saccharomyces cerevisiae acquires resistance to a lethal dose (5 mM) of MDA following prior exposure to a nonlethal concentration (1 mM). This response was completely inhibited by cycloheximide (50 microg ml(-1)), indicating a requirement for protein synthesis for adaptation. Furthermore, we have examined the roles of glutathione (GSH), mitochondrial function, and yAP-1-mediated transcription in conferring resistance and adaptation to MDA. A yap1 disruption mutant exhibited the greatest sensitivity and was unable to adapt to MDA, implicating yAP-1 in both the adaptive response and constitutive survival. The effect of MDA on GSH mutants indicated a role for GSH in initial resistance, whereas resistance acquired through adaptation was independent of GSH. Likewise, respiratory mutants (petite mutants) were sensitive to MDA but were still able to mount an adaptive response similar to that of the wild type, excluding mitochondria from any role in adaptation. MDA was detected in yeast cells by the thiobarbituric acid test and subsequent high-pressure liquid chromatography separation. Elevated levels were detected following treatment with hydrogen peroxide. However, the MDA-adaptive response was independent of that to H2O2.
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PMID:Saccharomyces cerevisiae exhibits a yAP-1-mediated adaptive response to malondialdehyde. 902 89

The aim of this work was to shed light on hypoxic and ischemic processes in the heart that may lead to irreversible or lethal myocardial injury. We determined malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities in human cardiac tissues from 45 medico-legal autopsies of persons who died from different causes. Samples were taken from three different areas of myocardium: the anterior and posterior walls of the left ventricle, and the interventricular septum. We used light microscopy to examine the heart sections (hematoxylin-eosin and Masson's trichromic stains), and studied the K+(Na+ ratio and pericardial fluid. A decrease in GSH-Px activity was found in cases with severe atherosclerosis of the coronary artery in comparison with the group with slight or moderate atherosclerosis. Postmortem activities of GSH-Px and SOD were significantly different in the three myocardial zones studied. An increase in GSH-Px activity in the interventricular septum was noted in cases of cardiac deaths. Antioxidant-related enzymes such as GSH-Px and SOD can therefore be regarded as new biochemical markers indicative of myocardial hypoxia. The possible applications to the postmortem diagnosis of the cause of death are discussed.
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PMID:Antioxidant-related enzymes in myocardial zones and human pericardial fluid in relation to the cause of death. 927 54

The effects of thiol compounds on oxidation of human low-density lipoprotein (LDL, 0.2 mg of protein/ml) by Cu2+ or Fe3+ (10 microM, each) were investigated in an in vitro system. L-Cysteine (CYS, 25 microM-1 mM) inhibited Cu2+-dependent, but facilitated Fe3+-dependent, oxidation of LDL in a dose-dependent manner. D,L-Homocysteine (HCY, 1 mM) and glutathione (GSH, 1 mM) similarly inhibited Cu2+-dependent, while facilitating Fe3+-dependent, oxidation of LDL. However, the effectiveness of these thiols (CYS, HCY, and GSH; 1 mM each) at mediating either Cu(2+)- or Fe3+-dependent LDL oxidation was not equivalent. Thus, Cu2+-dependent oxidation of LDL was most effectively inhibited by GSH, an intermediate effect was observed with HCY, and CYS was least effective. In contrast, a reversal of this pattern was observed for facilitation of Fe3+-dependent oxidation of LDL, with CYS being most effective and GSH being least effective. Interestingly, although the disulfides cystine and homocystine (0.5 mM, each) were without effect on either Cu(2+)- or Fe3+-dependent LDL oxidation, both glutathione disulfide (GSSG, 0.5 mM) and methionine (1 mM), an S-methylated derivative of HCY, inhibited Cu2+-dependent oxidation of LDL. However, neither GSSG nor methionine had any effect on Fe3+-dependent oxidation of LDL. Thus, while a free (reduced) thiol group is important for stimulation of Fe3+-dependent oxidation of LDL by CYS, HCY, and GSH, inhibition of Cu2+-dependent oxidation of LDL by these compounds seems to be thiol-independent. Our results show that thiol compounds differentially mediate Cu(2+)- and Fe3+-dependent LDL oxidation, an important early event in atherogenesis. Mediation of metal ion-dependent LDL oxidation by thiol compounds may have important implications for the etiology of atherosclerosis and may help explain the recent epidemiologic observation that plasma HCY concentration is an independent risk factor for cardiovascular disease.
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PMID:Physiological thiol compounds exert pro- and anti-oxidant effects, respectively, on iron- and copper-dependent oxidation of human low-density lipoprotein. 910 1


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