Original Article
Glutathione Peroxidase 1 Activity and Cardiovascular Events in Patients with Coronary Artery Disease
N Engl J Med 2003; 349:1605-1613October 23, 2003
- Abstract
Background
Cellular antioxidant enzymes such as glutathione peroxidase 1 and superoxide dismutase have a central role in the control of reactive oxygen species. In vitro data and studies in animal models suggest that these enzymes may protect against atherosclerosis, but little is known about their relevance to human disease.
Methods
We conducted a prospective study among 636 patients with suspected coronary artery disease, with a median follow-up period of 4.7 years (maximum, 5.4) to assess the risk of cardiovascular events associated with base-line erythrocyte glutathione peroxidase 1 and superoxide dismutase activity.
Results
Glutathione peroxidase 1 activity was among the strongest univariate predictors of the risk of cardiovascular events, whereas superoxide dismutase activity had no association with risk. The risk of cardiovascular events was inversely associated with increasing quartiles of glutathione peroxidase 1 activity (P for trend <0.001); patients in the highest quartile of glutathione peroxidase 1 activity had a hazard ratio of 0.29 (95 percent confidence interval, 0.15 to 0.58; P<0.001), as compared with those in the lowest quartile. Glutathione peroxidase 1 activity was affected by sex and smoking status but retained its predictive power in these subgroups. After adjustment for these and other cardiovascular risk factors, the inverse association between glutathione peroxidase 1 activity and cardiovascular events remained nearly unchanged.
Conclusions
In patients with coronary artery disease, a low level of activity of red-cell glutathione peroxidase 1 is independently associated with an increased risk of cardiovascular events. Glutathione peroxidase 1 activity may have prognostic value in addition to that of traditional risk factors. Furthermore, increasing glutathione peroxidase 1 activity might lower the risk of cardiovascular events.
Media in This Article
Figure 1
Kaplan–Meier Curves Showing Cardiovascular Events According to Quartile of Glutathione Peroxidase 1 Activity.Figure 2
Age- and Sex-Adjusted Hazard Ratios for Cardiovascular Events According to the Level of Glutathione Peroxidase 1 Activity and Smoking Status.Article Activity
- Article
Many aspects of the pathogenesis of atherosclerosis have been unraveled in recent years, and an important potential role of oxidative mechanisms has been elucidated.1,2 This research has led to the assumption that oxidation of low-density lipoprotein represents a key event in atherogenesis, even though the results of trials of antioxidants in the prevention of human atherosclerosis have been mostly negative.3
Oxidative stress may be defined as an imbalance between the production and degradation of reactive oxygen species such as superoxide anion, hydrogen peroxide, lipid peroxides, and peroxynitrite. Enzymatic inactivation of reactive oxygen species is achieved mainly by glutathione peroxidase, superoxide dismutase, and catalase.4 In mammalian cells, glutathione and the glutathione peroxidases constitute the principal antioxidant defense system.5,6 There are at least four different glutathione peroxidases, all of which contain selenocysteine at their active sites.7
Glutathione peroxidase 1, the ubiquitous intracellular form and key antioxidant enzyme within most cells, including the endothelium, uses glutathione to reduce hydrogen peroxide to water and lipid peroxides to their respective alcohols,8 and it also acts as a peroxynitrite reductase.9 In mice, glutathione peroxidase 1 deficiency results in abnormal vascular and cardiac function and structure.10 Similarly, superoxide dismutase is represented by three different ubiquitously expressed enzymes that convert superoxide anion to hydrogen peroxide: cytosolic copper- and zinc-containing superoxide dismutase, mitochondrial manganese-containing superoxide dismutase, and extracellular superoxide dismutase. Extracellular superoxide dismutase is most active in the vessel wall and has been shown to regulate the availability of nitric oxide by scavenging superoxide anion.11
On the basis of the experimental evidence, we addressed the hypothesis that enhanced activity of cellular glutathione peroxidase 1 and superoxide dismutase would be protective against cardiovascular events in a large prospective cohort of patients with coronary artery disease.
Methods
Study Population
Between November 1996 and December 1997, 732 patients referred to the Department of Medicine II of the Johannes Gutenberg University in Mainz, Germany, with suspected coronary artery disease were enrolled in the AtheroGene registry. Fourteen patients with acute myocardial infarction and 75 patients in whom glutathione peroxidase 1 activity could not be determined immediately were excluded from the present analysis. Thus, the final study cohort consisted of 643 patients, 133 with symptoms of unstable angina and 510 with symptoms of stable angina. Coronary angiography was performed in all patients. Relevant coronary artery disease, defined by greater than 30 percent stenosis in at least one major coronary artery, was detected in 558 patients. The study design has been described in detail elsewhere.12 The exclusion criteria were evidence of hemodynamically significant valvular heart disease, surgery or trauma within the previous month, known cardiomyopathy, known cancer, febrile conditions, or use of oral anticoagulant therapy within the previous four weeks.
We considered patients who were receiving dietary treatment or medication for diabetes or whose current fasting blood glucose level was above 125 mg per deciliter to have diabetes mellitus. Patients who had received antihypertensive treatment or who had received a diagnosis of hypertension (blood pressure above 160/90 mm Hg) were considered to have hypertension. Patients were classified as currently smoking, as having smoked in the past (if they had stopped more than 4 weeks and less than 40 years earlier), or as never having smoked (if they had never smoked or had stopped 40 or more years earlier).
Among the 643 patients, 636 (98.9 percent) were followed for a median of 4.7 years (maximum, 5.4). There were 64 deaths from cardiovascular causes, 21 deaths from other causes, and 19 nonfatal myocardial infarctions. Information about the causes of death and clinical events was obtained from hospital and general-practitioner charts.
The study was approved by the ethics committee of the University of Mainz. Participation was voluntary, and each patient gave written informed consent.
Laboratory Methods
Blood was drawn under standardized conditions before coronary angiography was performed. Glutathione peroxidase 1 activity and superoxide dismutase activity were determined in washed red cells obtained immediately after sampling from whole blood anticoagulated with EDTA. Hemolyzed cells were stored frozen for up to one week; freezing does not lead to changes in enzyme activity. Glutathione peroxidase 1 was measured as previously described,13 with minor modifications (Ransel test kit, Randox). The intraassay and interassay coefficients of variation were 6.7 percent and 9.9 percent, respectively.
Superoxide dismutase activity was determined by the following method. Superoxide radicals generated by the xanthine oxidase reaction convert 1-(4-iodophenyl)-3-(4-nitrophenol)-5-phenyltetrazolium chloride quantitatively to a formazan dye (Ransod test kit, Randox). Conversion of superoxide radicals to hydrogen peroxide by superoxide dismutase inhibits dye formation and serves as a measure of superoxide dismutase activity. The intraassay and interassay coefficients of variation were 5.1 percent and 5.5 percent, respectively. Serum lipid levels (the levels of total cholesterol, triglycerides, and high-density lipoprotein cholesterol) were measured immediately by routine methods; low-density lipoprotein cholesterol was calculated by the Friedewald formula.
For all other biologic markers measured in the study, plasma and serum were stored at –80°C until analysis, which was performed after a mean of 1.5 years of storage time. C-reactive protein was measured with a highly sensitive, latex-particle–enhanced immunoassay (Roche Diagnostics; range of detection, 0.1 to 20 mg per liter; interassay coefficient of variation, 1.0 percent for values of 15 mg per liter and 6.5 percent for values below 4 mg per liter). Interleukin-6 and soluble intercellular adhesion molecule 1 were measured with commercially available immunoassays (EASIA, Biosource Europe). Homocysteine was measured by high-pressure liquid chromatography (interassay coefficient of variation, 7.1 percent) and selenium by carbon-furnace atomic-absorption spectrometry with Zeeman compensation, as previously described.14
Statistical Analysis
The mean levels and proportions of base-line cardiovascular risk factors were calculated for study participants in whom a cardiovascular event subsequently occurred and in those without such an event. The significance of differences between the means for the two groups was assessed with Student's t-test, and the significance of differences in proportions was tested with the chi-square statistic. Variables with a skewed distribution were presented as medians, and the Wilcoxon rank-sum test was applied. The cumulative event plots according to quartile of glutathione peroxidase 1 activity were estimated by the Kaplan–Meier method and compared with use of the log-rank test. In all survival analyses, the end point was death from cardiovascular causes or nonfatal myocardial infarction. Data from patients who died from other causes were censored at the time of death. Hazard ratios for future coronary events according to quartile of glutathione peroxidase 1 activity were estimated by Cox regression models adjusted for potential confounders. Three adjusted models were constructed. We adjusted first for age and sex and second for other traditional risk factors. The final model included clinical and therapeutic variables as well as C-reactive protein, homocysteine, and creatinine.
To evaluate the combined effect of glutathione peroxidase 1 activity and smoking status on cardiovascular risk, we divided the study participants into six groups according to whether the glutathione peroxidase 1 activity was above the median or at or below the median and according to their smoking-status category. In these analyses, Cox regression was used to assess simultaneously the risk of future cardiovascular events in each of the six groups, with the group of patients whose glutathione peroxidase 1 activity was above the median and who had never smoked as the reference group. The hypothesis that smoking and the level of glutathione peroxidase 1 activity had an interactive effect on the risk of future cardiovascular events was formally tested in a Cox regression model that included a term for the multiplicative interaction of smoking (across the three categories of smoking status) and glutathione peroxidase 1 activity. The hazard ratios and their 95 percent confidence intervals are reported. The P values are two-sided; a P value of less than 0.05 was considered to indicate statistical significance. All computations were carried out with SPSS software, version 10.07.
Results
Table 1Table 1
Base-Line Characteristics of the Study Patients. gives the base-line characteristics of the 83 study participants who subsequently died from cardiovascular causes or had a nonfatal myocardial infarction and the 553 who did not have a cardiovascular event, including the results of base-line blood-chemistry analysis. Glutathione peroxidase 1 activity was normally distributed among the study participants. It ranged from 7.4 to 99.6 units per gram of hemoglobin, with a mean (±SD) of 49.2±11.6, a median of 48.3, and an interquartile range of 42.0 to 56.3 units per gram of hemoglobin. The base-line level of glutathione peroxidase 1 activity was significantly lower among those who died from cardiac causes or had a nonfatal myocardial infarction than among those who did not. This result was stable when data from the subgroups with fatal events (64 patients) and nonfatal events (19 patients) were analyzed separately (45.7±13.5 and 44.1±10.4 units per gram of hemoglobin, respectively, vs. 49.8±11.3 units per gram of hemoglobin for those who did not have cardiovascular events or die from noncardiovascular causes; P=0.009 and P=0.03, respectively). The base-line level of glutathione peroxidase 1 activity in patients who died from noncardiovascular causes (21 patients) was the same as that in event-free patients (49.7±11.1 vs. 49.8±11.3 units per gram of hemoglobin).Figure 1Figure 1
Kaplan–Meier Curves Showing Cardiovascular Events According to Quartile of Glutathione Peroxidase 1 Activity. shows the Kaplan–Meier curves for event-free survival according to quartile of glutathione peroxidase 1 activity. The unadjusted rate of cardiovascular events increased in a stepwise fashion across decreasing quartiles of base-line glutathione peroxidase 1 activity. The difference between the lowest and highest quartiles and the trend across all quartiles were significant (P<0.001 for both comparisons). The event rate for patients in the lowest quartile of glutathione peroxidase 1 activity (20.8 percent) was approximately three times that for patients in the highest quartile (7.0 percent). To place the effect in perspective, Table 2Table 2
Age- and Sex-Adjusted Analysis of the Association between Novel and Traditional Risk Factors and the Risk of a Cardiovascular Event. presents the hazard ratios for cardiovascular events associated with an increase of 1 SD in various risk factors.The strongest predictors of the level of glutathione peroxidase 1 activity were smoking status and sex. Significantly lower levels of glutathione peroxidase 1 activity were observed in current smokers than in those who had never smoked (45.7 vs. 51.6 units per gram of hemoglobin, P<0.001). Former smokers also had lower levels of enzyme activity than those who had never smoked (48.2 vs. 51.6 units per gram of hemoglobin); however, this difference was not statistically significant. Furthermore, the level of glutathione peroxidase 1 activity was lower in men than in women (48.5 vs. 51.1 units per gram of hemoglobin, P=0.009). Women below 55 years of age had higher levels of glutathione peroxidase 1 activity than older women (54.1 vs. 50.5 units per gram of hemoglobin, P=0.12). No difference in glutathione peroxidase 1 activity was detected between patients with stable angina and those with unstable angina.
Although statin medication had no significant association with glutathione peroxidase 1 activity in the whole study population, the percentage of patients receiving statins was significantly higher among those in the highest quartile of glutathione peroxidase 1 activity than among those in the other three quartiles (30.6 percent vs. 19.5 percent, P=0.003). With this exception, no association was observed between the use of any cardiovascular medication and glutathione peroxidase 1 or superoxide dismutase activity. There was a weak but significant correlation of glutathione peroxidase 1 activity with homocysteine (r=–0.09, P=0.03) and selenium (r=0.09, P=0.04). Of all the inflammatory markers measured in this study, only soluble intercellular adhesion molecule 1 showed a moderate inverse correlation with glutathione peroxidase 1 activity (r=–0.11, P=0.02).
To assess the independent predictive value of glutathione peroxidase 1 activity, we used a series of Cox predictive models (Table 3Table 3
Hazard Ratios for Future Cardiovascular Events According to Quartile of Base-Line Glutathione Peroxidase 1 Activity.). The inverse relation between glutathione peroxidase 1 activity and relative risk remained nearly unchanged after adjustment for cardiovascular risk factors and clinical features (model 2). Further adjustment for therapeutic variables as well as C-reactive protein (as a cluster representative of the inflammatory markers), homocysteine, and creatinine (model 3) also did not attenuate the relative risk associated with glutathione peroxidase 1 activity; patients in the highest quartile of glutathione peroxidase 1 activity had a hazard ratio of 0.29 (95 percent confidence interval, 0.14 to 0.60; P=0.001) as compared with those in the lowest quartile. Inclusion of interleukin-6 instead of C-reactive protein in the Cox predictive model had no effect on the hazard ratios. Similarly, in a subgroup of 566 patients in whom the ejection fraction had been measured, adjustment for this variable did not alter the hazard ratio associated with increasing quartiles of glutathione peroxidase 1 activity (data not shown).In previous reports from the entire AtheroGene cohort, the levels of several inflammatory markers, such as interleukin-18 and soluble vascular adhesion molecule 1, were found to be elevated among those at risk for subsequent coronary events. No statistically significant correlations were observed between glutathione peroxidase 1 activity and these two proteins. Inclusion of these variables in multivariate analyses did not attenuate the risk of future coronary events associated with decreased levels of glutathione peroxidase 1 activity.
Because smoking status was associated with base-line glutathione peroxidase 1 activity as well as with coronary risk, the interaction between smoking status and glutathione peroxidase 1 activity was analyzed in more detail. The association between smoking and cardiovascular events was observed predominantly in patients with levels of glutathione peroxidase 1 activity below the median. As illustrated in Figure 2Figure 2
Age- and Sex-Adjusted Hazard Ratios for Cardiovascular Events According to the Level of Glutathione Peroxidase 1 Activity and Smoking Status., among those with low levels of glutathione peroxidase 1 activity (at or below the median value of 48.32 units per gram of hemoglobin), former smokers were at significant risk for cardiovascular events (hazard ratio, 3.0, as compared with patients who had never smoked and had high glutathione peroxidase 1 activity; 95 percent confidence interval, 1.5 to 5.9; P=0.001), as were current smokers (hazard ratio, 5.6; 95 percent confidence interval, 2.4 to 13.5; P<0.001). To a lesser extent, a significant increase in cardiovascular risk was also observed in former or current smokers in the subgroup of those with levels of glutathione peroxidase 1 activity above the median.Discussion
In this prospective cohort of patients with angiographically documented coronary artery disease, we demonstrated that erythrocyte intracellular glutathione peroxidase 1 activity is inversely associated with future fatal and nonfatal cardiovascular events. Erythrocyte glutathione peroxidase 1 is probably a suitable surrogate marker for cellular glutathione peroxidase 1 activity in general, but this has not been proved by a systematic analysis. The risk of a cardiovascular event among those in the highest quartile of glutathione peroxidase 1 activity was approximately 30 percent of that among those in the lowest quartile. This difference did not change appreciably after adjustment for most potential confounders, indicating that the relation between glutathione peroxidase 1 and future cardiovascular events is independent of other risk factors and clinical features.
Because glutathione peroxidase 1 appears to have a major role in the prevention of oxidative stress, it may also be an important antiatherogenic enzyme.2 In fact, reduced expression of glutathione peroxidase 1 has been shown to increase cell-mediated oxidation of low-density lipoprotein in mice.15 Furthermore, mice that are heterozygous for glutathione peroxidase 1 deficiency have endothelial dysfunction combined with structural vascular abnormalities, such as increased periadventitial inflammation, neointimal formation, and collagen deposition surrounding the coronary arteries.10 Glutathione peroxidase 1 deficiency apparently decreases bioavailable nitric oxide in mice,16 an effect that can be aggravated by hyperhomocysteinemia.17 In addition, glutathione peroxidase 1 activity is decreased or absent in carotid atherosclerotic plaques, and the lack of glutathione peroxidase 1 activity in atherosclerotic lesions appears to be associated with the development of more severe lesions in humans.18 Since catalase activity is absent from human vascular cells19 and superoxide dismutase is poorly effective against cellular oxidant damage,6 the most important antioxidative shield is reduced in atherosclerotic plaque.
The variability in glutathione peroxidase 1 activity within an individual patient has been reported to be about half the variability between patients,20 which is in accordance with our own observations (unpublished data). The causes of variability between patients are not well established. The few genetic polymorphisms identified so far do not show an association with glutathione peroxidase 1 activity.21 Smoking consistently reduces glutathione peroxidase 1 activity, whereas the effect of commonly used drugs appears to be negligible.20 The level of glutathione peroxidase 1 activity is higher in women than in men. In our study this difference was most pronounced in premenopausal women, as has been described previously.22
Cigarette smoking is strongly associated with dysfunctional vasomotor responses, diminished nitric oxide levels, and time-dependent decreases in the content of endothelial nitric oxide synthase messenger RNA.23 In accordance with previous studies,24 glutathione peroxidase 1 activity was decreased in smokers and former smokers. However, the association between low levels of glutathione peroxidase 1 activity and high cardiovascular risk was also observed in smokers. Therefore, measurement of glutathione peroxidase 1 should identify smokers who are at highest risk for cardiovascular events.
Glutathione peroxidase 1 was recently shown to inhibit 5-lipoxygenase in monocytic cells.25 Since 5-lipoxygenase is induced in monocytes and macrophages within progressing atherosclerotic lesions26 and strongly contributes to atherosclerotic susceptibility in mice,27 the interference of glutathione peroxidase 1 with 5-lipoxygenase might constitute a protective function of the enzyme, in addition to its antioxidant activity.
The role of selenium, which is known to increase glutathione peroxidase 1 gene expression and activity,28,29 in cardiovascular disease is controversial. Epidemiologic studies have been inconclusive,30-32 and prospective, controlled trials of selenium supplementation are lacking.33 In the present study, a weak but statistically significant association was observed between selenium levels and glutathione peroxidase 1 activity. The weakness of this association might be due to the fact that the average selenium level was above 70 ng per milliliter, which is probably within the range where the effect of selenium on glutathione peroxidase 1 activity plateaus.34,35
From a clinical perspective, our data show that low erythrocyte glutathione peroxidase 1 activity identifies patients with coronary artery disease who are at the highest risk for cardiovascular events. Adjustment for inflammatory markers such as soluble adhesion molecules or interleukin-18, which have been shown to be predictive of cardiovascular events in this study population,36,37 does not affect the association between glutathione peroxidase 1 and prognosis. This observation suggests that measurement of glutathione peroxidase 1 activity provides additional information on risk and might be useful in identifying patients who would benefit from preventive antioxidative treatment.
Supported by grants from the Stiftung Rheinland-Pfalz für Innovation, Ministry for Science and Education, Mainz, Germany (AZ 15202-386261/545); INSERM, Paris (to Dr. Blankenberg), and the Schleicher Stiftung, Dresdner Bank, Frankfurt, Germany.
Source Information
From the Departments of Medicine II (S.B., H.J.R., J.M.) and Clinical Chemistry and Laboratory Medicine (M.T., G.H., K.J.L.), Johannes Gutenberg University, Mainz, Germany; INSERM Unité 525, Faculté de Médecine Pitié–Salpêtrière, Paris (S.B., L.T., F.C.); Innere Abteilung, Bundeswehrzentralkrankenhaus, Koblenz, Germany (C.B.); and the Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ont., Canada (M.S.).
Address reprint requests to Dr. Blankenberg at the Department of Medicine II or to Dr. Lackner at the Department of Clinical Chemistry and Laboratory Medicine, Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany, or to stefan.blankenberg@uni-mainz.de or lackner@zentrallabor.klinik.uni-mainz.de.
Members of the AtheroGene study group are listed in the Appendix.
Appendix
The other members of the AtheroGene study group are as follows: Department of Medicine II, Johannes Gutenberg University, Mainz, Germany — C. Espinola-Klein; INSERM Unité 525, Paris — O. Poirier, V. Nicaud, D. Tregouet, and J.-L. Georges. AtheroGene recruitment centers were the Department of Medicine II, Johannes Gutenberg University, Mainz, Germany, and Innere Abteilung, Bundeswehrzentralkrankenhaus, Koblenz, Germany.
- References
References
1
Ross R . Atherosclerosis -- an inflammatory disease. N Engl J Med 1999;340:115-126
Full Text | Web of Science | Medline2
Glass CK ,Witztum JL . Atherosclerosis: the road ahead. Cell 2001;104:503-516
CrossRef | Web of Science | Medline3
Steinberg D ,Witztum JL . Is the oxidative modification hypothesis relevant to human atherosclerosis? Do the antioxidant trials conducted to date refute the hypothesis? Circulation 2002;105:2107-2111
CrossRef | Web of Science | Medline4
Forsberg L ,de Faire U ,Morgenstern R . Oxidative stress, human genetic variation, and disease. Arch Biochem Biophys 2001;389:84-93
CrossRef | Web of Science | Medline5
Ursini F ,Maiorino M ,Brigelius-Flohe R , et al. Diversity of glutathione peroxidases. Methods Enzymol 1995;252:38-53
CrossRef | Web of Science | Medline6
Raes M ,Michiels C ,Remacle J . Comparative study of the enzymatic defense systems against oxygen-derived free radicals: the key role of glutathione peroxidase. Free Radic Biol Med 1987;3:3-7
CrossRef | Web of Science | Medline7
Arthur JR . The glutathione peroxidases. Cell Mol Life Sci 2000;57:1825-1835
CrossRef | Web of Science | Medline8
Flohe L . Glutathione peroxidase. Basic Life Sci 1988;49:663-668
Medline9
Sies H . Glutathione and its role in cellular functions. Free Radic Biol Med 1999;27:916-921
CrossRef | Web of Science | Medline10
Forgione MA ,Cap A ,Liao R , et al. Heterozygous cellular glutathione peroxidase deficiency in the mouse: abnormalities in vascular and cardiac function and structure. Circulation 2002;106:1154-1158
CrossRef | Web of Science | Medline11
Fukai T ,Folz RJ ,Landmesser U ,Harrison DG . Extracellular superoxide dismutase and cardiovascular disease. Cardiovasc Res 2002;55:239-249
CrossRef | Web of Science | Medline12
Rupprecht HJ ,Blankenberg S ,Bickel C , et al. Impact of viral and bacterial infectious burden on long-term prognosis in patients with coronary artery disease. Circulation 2001;104:25-31
CrossRef | Web of Science | Medline13
Paglia DE ,Valentine WN . Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967;70:158-169
Medline14
Oster O ,Prellwitz W . A methodological comparison of hydride and carbon furnace atomic absorption spectroscopy for the determination of selenium in serum. Clin Chim Acta 1982;124:277-291
CrossRef | Web of Science | Medline15
Guo Z ,Van Remmen H ,Yang H , et al. Changes in expression of antioxidant enzymes affect cell-mediated LDL oxidation and oxidized LDL-induced apoptosis in mouse aortic cells. Arterioscler Thromb Vasc Biol 2001;21:1131-1138
CrossRef | Web of Science | Medline16
Forgione MA ,Weiss N ,Heydrick S , et al. Cellular glutathione peroxidase deficiency and endothelial dysfunction. Am J Physiol Heart Circ Physiol 2002;282:H1255-H1261
Web of Science | Medline17
Dayal S ,Brown KL ,Weydert CJ , et al. Deficiency of glutathione peroxidase-1 sensitizes hyperhomocysteinemic mice to endothelial dysfunction. Arterioscler Thromb Vasc Biol 2002;22:1996-2002
CrossRef | Web of Science | Medline18
Lapenna D ,de Gioia S ,Ciofani G , et al. Glutathione-related antioxidant defenses in human atherosclerotic plaques. Circulation 1998;97:1930-1934
Web of Science | Medline19
Shingu M ,Yoshioka K ,Nobunaga M ,Yoshida K . Human vascular smooth muscle cells and endothelial cells lack catalase activity and are susceptible to hydrogen peroxide. Inflammation 1985;9:309-320
CrossRef | Web of Science | Medline20
Andersen HR ,Nielsen JB ,Nielsen F ,Grandjean P . Antioxidative enzyme activities in human erythrocytes. Clin Chem 1997;43:562-568
Web of Science | Medline21
Forsberg L ,de Faire U ,Marklund SL ,Andersson PM ,Stegmayr B ,Morgenstern R . Phenotype determination of a common Pro-Leu polymorphism in human glutathione peroxidase 1. Blood Cells Mol Dis 2000;26:423-426
CrossRef | Web of Science | Medline22
Massafra C ,Gioia D ,De Felice C ,Muscettola M ,Longini M ,Buonocore G . Gender-related differences in erythrocyte glutathione peroxidase activity in healthy subjects. Clin Endocrinol (Oxf) 2002;57:663-667
CrossRef | Web of Science | Medline23
Su Y ,Han W ,Giraldo C ,De Li Y ,Block ER . Effect of cigarette smoke extract on nitric oxide synthase in pulmonary artery endothelial cells. Am J Respir Cell Mol Biol 1998;19:819-825
Web of Science | Medline24
Mulholland CW ,Elwood PC ,Davis A , et al. Antioxidant enzymes, inflammatory indices and lifestyle factors in older men: a cohort analysis. QJM 1999;92:579-585
CrossRef | Medline25
Straif D ,Werz O ,Kellner R ,Bahr U ,Steinhilber D . Glutathione peroxidase-1 but not -4 is involved in the regulation of cellular 5-lipoxygenase activity in monocytic cells. Biochem J 2000;349:455-461
CrossRef | Web of Science | Medline26
Spanbroek R ,Grabner R ,Lotzer K , et al. Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis. Proc Natl Acad Sci U S A 2003;100:1238-1243
CrossRef | Web of Science | Medline27
Mehrabian M ,Allayee H ,Wong J , et al. Identification of 5-lipoxygenase as a major gene contributing to atherosclerosis susceptibility in mice. Circ Res 2002;91:120-126[Erratum, Circ Res 2002;91:e27.]
CrossRef | Web of Science | Medline28
Hussein O ,Rosenblat M ,Refael G ,Aviram M . Dietary selenium increases cellular glutathione peroxidase activity and reduces the enhanced susceptibility to lipid peroxidation of plasma and low-density lipoprotein in kidney transplant recipients. Transplantation 1997;63:679-685
CrossRef | Web of Science | Medline29
Liu D ,Liu S ,Huang Y ,Liu Y ,Zhang Z ,Han L . Effect of selenium on human myocardial glutathione peroxidase gene expression. Chin Med J (Engl) 2000;113:771-775
Web of Science | Medline30
Salonen JT ,Salonen R ,Seppanen K , et al. Relationship of serum selenium and antioxidants to plasma lipoproteins, platelet aggregability and prevalent ischaemic heart disease in Eastern Finnish men. Atherosclerosis 1988;70:155-160
CrossRef | Web of Science | Medline31
Suadicani P ,Hein HO ,Gyntelberg F . Serum selenium concentration and risk of ischaemic heart disease in a prospective cohort study of 3000 males. Atherosclerosis 1992;96:33-42
CrossRef | Web of Science | Medline32
Salvini S ,Hennekens CH ,Morris JS ,Willett WC ,Stampfer MJ . Plasma levels of the antioxidant selenium and risk of myocardial infarction among U.S. physicians. Am J Cardiol 1995;76:1218-1221
CrossRef | Web of Science | Medline33
Rayman MP . The importance of selenium to human health. Lancet 2000;356:233-241
CrossRef | Web of Science | Medline34
Alissa EM ,Bahijri SM ,Ferns GA . The controversy surrounding selenium and cardiovascular disease: a review of the evidence. Med Sci Monit 2003;9:RA9-RA18
Medline35
Kardinaal AF ,Kok FJ ,Kohlmeier L , et al. Association between toenail selenium and risk of acute myocardial infarction in European men: the EURAMIC Study: European Antioxidant Myocardial Infarction and Breast Cancer. Am J Epidemiol 1997;145:373-379
Web of Science | Medline36
Blankenberg S ,Tiret L ,Bickel C , et al. Interleukin-18 is a strong predictor of cardiovascular death in stable and unstable angina. Circulation 2002;106:24-30
CrossRef | Web of Science | Medline37
Blankenberg S ,Rupprecht HJ ,Bickel C , et al. Circulating cell adhesion molecules and death in patients with coronary artery disease. Circulation 2001;104:1336-1342
CrossRef | Web of Science | Medline
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Maysam Takapoo, Ali H. Chamseddine, Ramesh C. Bhalla, Francis J. Miller. (2011) Glutathione peroxidase-deficient smooth muscle cells cause paracrine activation of normal smooth muscle cells via cyclophilin A. Vascular Pharmacology
CrossRef14
Deniz Cemgil Arikan, Ayhan Coskun, Ali Ozer, Metin Kilinc, Filiz Atalay, Tugba Arikan. (2011) Plasma Selenium, Zinc, Copper and Lipid Levels in Postmenopausal Turkish Women and Their Relation with Osteoporosis. Biological Trace Element Research
CrossRef15
Dan Farbstein, Yitzchak Z. Soloveichik, Nina S. Levy, Andrew P. Levy. (2011) Genetics of Redox Systems and Their Relationship with Cardiovascular Disease. Current Atherosclerosis Reports 13:3, 215-224
CrossRef16
Rosaria Varì, Massimo D'Archivio, Carmelina Filesi, Simona Carotenuto, Beatrice Scazzocchio, Carmela Santangelo, Claudio Giovannini, Roberta Masella. (2011) Protocatechuic acid induces antioxidant/detoxifying enzyme expression through JNK-mediated Nrf2 activation in murine macrophages. The Journal of Nutritional Biochemistry 22:5, 409-417
CrossRef17
J. C. Charniot, A. Sutton, D. Bonnefont-Rousselot, C. Cosson, R. Khani-Bittar, P. Giral, N. Charnaux, J. P. Albertini. (2011) Manganese superoxide dismutase dimorphism relationship with severity and prognosis in cardiogenic shock due to dilated cardiomyopathy. Free Radical Research 45:4, 379-388
CrossRef18
Michael Maes, Piyanuj Ruckoanich, Young Seun Chang, Nithi Mahanonda, Michael Berk. (2011) Multiple aberrations in shared inflammatory and oxidative & nitrosative stress (IO&NS) pathways explain the co-association of depression and cardiovascular disorder (CVD), and the increased risk for CVD and due mortality in depressed patients. Progress in Neuro-Psychopharmacology and Biological Psychiatry 35:3, 769-783
CrossRef19
Shin-ichiro Tanaka, Tetsuo Miki, Shoto Sha, Ken-ichi Hirata, Yuichi Ishikawa, Mitsuhiro Yokoyama. (2011) Serum Levels of Thiobarbituric Acid-Reactive Substances are Associated with Risk of Coronary Heart Disease. Journal of Atherosclerosis and Thrombosis 18:7, 584-591
CrossRef20
Sunan Wang, John P. Melnyk, Rong Tsao, Massimo F. Marcone. (2011) How natural dietary antioxidants in fruits, vegetables and legumes promote vascular health. Food Research International 44:1, 14-22
CrossRef21
Yaling Yang, Sze Wa Chan, Miao Hu, Richard Walden, Brian Tomlinson. (2011) Effects of Some Common Food Constituents on Cardiovascular Disease. ISRN Cardiology 2011, 1-16
CrossRef22
Annateresa Papazzo, Xavier A Conlan, Louise Lexis, Paul A Lewandowski. (2011) Differential effects of dietary canola and soybean oil intake on oxidative stress in stroke-prone spontaneously hypertensive rats. Lipids in Health and Disease 10:1, 98
CrossRef23
Annateresa Papazzo, Xavier Conlan, Louise Lexis, Paul Lewandowski. (2011) The effect of short-term canola oil ingestion on oxidative stress in the vasculature of stroke-prone spontaneously hypertensive rats. Lipids in Health and Disease 10:1, 180
CrossRef24
T.S. Tang, S.L. Prior, K.W. Li, H.A. Ireland, S.C. Bain, S.J. Hurel, J.A. Cooper, S.E. Humphries, J.W. Stephens. (2010) Association between the rs1050450 glutathione peroxidase-1 (C > T) gene variant and peripheral neuropathy in two independent samples of subjects with diabetes mellitus. Nutrition, Metabolism and Cardiovascular Diseases
CrossRef25
S. Stranges, A. Navas-Acien, M.P. Rayman, E. Guallar. (2010) Selenium status and cardiometabolic health: State of the evidence. Nutrition, Metabolism and Cardiovascular Diseases 20:10, 754-760
CrossRef26
Yu. A. Shuvalova, A. I. Kaminnyi, A. N. Meshkov, V. V. Kukharchuk. (2010) Pro198Leu Polymorphism of GPx-1 Gene and Activity of Erythrocytic Glutathione Peroxidase and Lipid Peroxidation Products. Bulletin of Experimental Biology and Medicine 149:6, 743-745
CrossRef27
Sara Tucci, Sonja Primassin, Ute Spiekerkoetter. (2010) Fasting-induced oxidative stress in very long chain acyl-CoA dehydrogenase-deficient mice. FEBS Journal 277:22, 4699-4708
CrossRef28
S.G. Donaldson, J. Van Oostdam, C. Tikhonov, M. Feeley, B. Armstrong, P. Ayotte, O. Boucher, W. Bowers, L. Chan, F. Dallaire, R. Dallaire, É. Dewailly, J. Edwards, G.M. Egeland, J. Fontaine, C. Furgal, T. Leech, E. Loring, G. Muckle, T. Nancarrow, D. Pereg, P. Plusquellec, M. Potyrala, O. Receveur, R.G. Shearer. (2010) Environmental contaminants and human health in the Canadian Arctic. Science of The Total Environment 408:22, 5165-5234
CrossRef29
Robyn S. Lymbury, Matthew J. Marino, Anthony V. Perkins. (2010) Effect of dietary selenium on the progression of heart failure in the ageing spontaneously hypertensive rat. Molecular Nutrition & Food Research 54:10, 1436-1444
CrossRef30
Sayuri Miyamoto, Hirofumi Arai, Junji Terao. 2010. Enzymatic Antioxidant Defenses. , 21-33.
CrossRef31
Eugene A Podrez. (2010) Anti-oxidant properties of high-density lipoprotein and atherosclerosis. Clinical and Experimental Pharmacology and Physiology 37:7, 719-725
CrossRef32
Cong Lei, Xiaolin Niu, Xiangke Ma, Jin Wei. (2010) Is selenium deficiency really the cause of Keshan disease?. Environmental Geochemistry and Health
CrossRef33
Chun-Seok Cho, Sukmook Lee, Geun Taek Lee, Hyun Ae Woo, Eui-Ju Choi, Sue Goo Rhee. (2010) Irreversible Inactivation of Glutathione Peroxidase 1 and Reversible Inactivation of Peroxiredoxin II by H 2 O 2 in Red Blood Cells. Antioxidants & Redox Signaling 12:11, 1235-1246
CrossRef34
Ulrich Förstermann. (2010) Nitric oxide and oxidative stress in vascular disease. Pflügers Archiv - European Journal of Physiology 459:6, 923-939
CrossRef35
Marcus Conrad, Ulrich Schweizer. (2010) Unveiling the Molecular Mechanisms Behind Selenium-Related Diseases Through Knockout Mouse Studies. Antioxidants & Redox Signaling 12:7, 851-865
CrossRef36
Edith Lubos, Christoph R. Sinning, Renate B. Schnabel, Philipp S. Wild, Tanja Zeller, Hans J. Rupprecht, Christoph Bickel, Karl J. Lackner, Dirk Peetz, Joseph Loscalzo, Thomas Münzel, Stefan Blankenberg. (2010) Serum selenium and prognosis in cardiovascular disease: results from the AtheroGene study. Atherosclerosis 209:1, 271-277
CrossRef37
V. V. Shumyantseva, E. V. Suprun, T. V. Bulko, O. V. Dobrynina, A. I. Archakov. (2010) Sensor systems for medical application based on hemoproteins and nanocomposite materials. Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry 4:1, 25-36
CrossRef38
María Isabel Covas, Philippe Gambert, Montserrat Fitó, Rafael de la Torre. (2010) Wine and oxidative stress: Up-to-date evidence of the effects of moderate wine consumption on oxidative damage in humans. Atherosclerosis 208:2, 297-304
CrossRef39
Jose T. Real, Sergio Martínez-Hervás, M. Carmen Tormos, Elena Domenech, Federico V. Pallardó, Guillermo Sáez-Tormo, Josep Redon, Rafael Carmena, F. Javier Chaves, Juan F. Ascaso, Ana-Barbara García-García. (2010) Increased oxidative stress levels and normal antioxidant enzyme activity in circulating mononuclear cells from patients of familial hypercholesterolemia. Metabolism 59:2, 293-298
CrossRef40
Andreja Sinkovic, David Suran, Lidija Lokar, Eva Fliser, Mojca Skerget, Zoran Novak, Zeljko Knez. (2010) Rosemary extracts improve flow-mediated dilatation of the brachial artery and plasma PAI-1 activity in healthy young volunteers. Phytotherapy Researchn/a-n/a
CrossRef41
Jane A. Leopold, Joseph Loscalzo. (2009) Oxidative risk for atherothrombotic cardiovascular disease. Free Radical Biology and Medicine 47:12, 1673-1706
CrossRef42
Akihiro Isogawa, Minoru Yamakado, Masao Yano, Teruo Shiba. (2009) Serum superoxide dismutase activity correlates with the components of metabolic syndrome or carotid artery intima-media thickness. Diabetes Research and Clinical Practice 86:3, 213-218
CrossRef43
Lutz Schomburg, Ulrich Schweizer. (2009) Hierarchical regulation of selenoprotein expression and sex-specific effects of selenium. Biochimica et Biophysica Acta (BBA) - General Subjects 1790:11, 1453-1462
CrossRef44
Holger Steinbrenner, Helmut Sies. (2009) Protection against reactive oxygen species by selenoproteins. Biochimica et Biophysica Acta (BBA) - General Subjects 1790:11, 1478-1485
CrossRef45
Margaret P. Rayman. (2009) Selenoproteins and human health: Insights from epidemiological data. Biochimica et Biophysica Acta (BBA) - General Subjects 1790:11, 1533-1540
CrossRef46
Jun Lu, Carsten Berndt, Arne Holmgren. (2009) Metabolism of selenium compounds catalyzed by the mammalian selenoprotein thioredoxin reductase. Biochimica et Biophysica Acta (BBA) - General Subjects 1790:11, 1513-1519
CrossRef47
Alison M Hill, Jennifer A Fleming, Penny M Kris-Etherton. (2009) The role of diet and nutritional supplements in preventing and treating cardiovascular disease. Current Opinion in Cardiology 24:5, 433-441
CrossRef48
G. Flores-Mateo, P. Carrillo-Santisteve, R. Elosua, E. Guallar, J. Marrugat, J. Bleys, M.-I. Covas. (2009) Antioxidant Enzyme Activity and Coronary Heart Disease: Meta-analyses of Observational Studies. American Journal of Epidemiology 170:2, 135-147
CrossRef49
Christian K. Roberts, Kunal K. Sindhu. (2009) Oxidative stress and metabolic syndrome. Life Sciences 84:21-22, 705-712
CrossRef50
Absalon D. Gutierrez, Daniela Gonzalez de Serna, Irina Robinson, David S. Schade. (2009) The response of γ vitamin E to varying dosages of α vitamin E plus vitamin C. Metabolism 58:4, 469-478
CrossRef51
Reiko Iida, Etsuko Tsubota, Isao Yuasa, Haruo Takeshita, Toshihiro Yasuda. (2009) Simultaneous genotyping of 11 non-synonymous SNPs in the 4 glutathione peroxidase genes using the multiplex single base extension method. Clinica Chimica Acta 402:1-2, 79-82
CrossRef52
Kallol Dutta, Biswadev Bishayi. (2009) Escherichia coli lipopolysaccharide administration alters antioxidant profile during hypercholesterolemia. Indian Journal of Clinical Biochemistry 24:2, 179-183
CrossRef53
Pilar Codoñer-Franch, Amalia Bataller Alberola, José V. Domingo Camarasa, María C. Escribano Moya, Victoria Valls Bellés. (2009) Influence of dietary lipids on the erythrocyte antioxidant status of hypercholesterolaemic children. European Journal of Pediatrics 168:3, 321-327
CrossRef54
Mei-ling Cheng, Chin-ming Chen, Hung-yao Ho, Jui-ming Li, Daniel Tsun-yee Chiu. (2009) Effect of Acute Myocardial Infarction on Erythrocytic Glutathione Peroxidase 1 Activity and Plasma Vitamin E Levels. The American Journal of Cardiology 103:4, 471-475
CrossRef55
Cong Lei, Xiaolin Niu, Jin Wei, Jianhong Zhu, Yi Zhu. (2009) Interaction of glutathione peroxidase-1 and selenium in endemic dilated cardiomyopathy. Clinica Chimica Acta 399:1-2, 102-108
CrossRef56
R D Semba, M O Ricks, L Ferrucci, Q-L Xue, J M Guralnik, L P Fried. (2009) Low serum selenium is associated with anemia among older adults in the United States. European Journal of Clinical Nutrition 63:1, 93-99
CrossRef57
Robyn Lymbury, Ujang Tinggi, Lyn Griffiths, Franklin Rosenfeldt, Anthony V. Perkins. (2008) Selenium Status of the Australian Population: Effect of Age, Gender and Cardiovascular Disease. Biological Trace Element Research 126:S1, 1-10
CrossRef58
Renate Schnabel, Edith Lubos, Claudia M. Messow, Christoph R. Sinning, Tanja Zeller, Philipp S. Wild, Dirk Peetz, Diane E. Handy, Thomas Munzel, Joseph Loscalzo, Karl J. Lackner, Stefan Blankenberg. (2008) Selenium supplementation improves antioxidant capacity in vitro and in vivo in patients with coronary artery disease. American Heart Journal 156:6, 1201.e1-1201.e11
CrossRef59
Lutz Schomburg, Josef Köhrle. (2008) On the importance of selenium and iodine metabolism for thyroid hormone biosynthesis and human health. Molecular Nutrition & Food Research 52:11, 1235-1246
CrossRef60
Yu-I Li, Gary Elmer, Renée C. LeBoeuf. (2008) Tanshinone IIA reduces macrophage death induced by hydrogen peroxide by upregulating glutathione peroxidase. Life Sciences 83:15-16, 557-562
CrossRef61
T. Keller, C. M. Messow, E. Lubos, V. Nicaud, P. S. Wild, H. J. Rupprecht, C. Bickel, S. Tzikas, D. Peetz, K. J. Lackner, L. Tiret, T. F. Munzel, S. Blankenberg, R. B. Schnabel. (2008) Cystatin C and cardiovascular mortality in patients with coronary artery disease and normal or mildly reduced kidney function: results from the AtheroGene study. European Heart Journal 30:3, 314-320
CrossRef62
Fares A. Masri, Suzy A. A. Comhair, Iva Dostanic-Larson, Francisco Takao Kaneko, Raed A. Dweik, Alejandro C. Arroliga, Serpil C. Erzurum. (2008) Deficiency of Lung Antioxidants in Idiopathic Pulmonary Arterial Hypertension. Clinical and Translational Science 1:2, 99-106
CrossRef63
Na-Ping Tang, Lian-Sheng Wang, Li Yang, Hai-Juan Gu, Qing-Min Sun, Ri-Hong Cong, Bo Zhou, Huai-Jun Zhu, Bin Wang. (2008) Genetic variant in glutathione peroxidase 1 gene is associated with an increased risk of coronary artery disease in a Chinese population. Clinica Chimica Acta 395:1-2, 89-93
CrossRef64
Sergio Martinez-Hervas, Marta Fandos, Jose T. Real, Olga Espinosa, F. Javier Chaves, Guillermo T. Saez, Amparo Salvador, Concha Cerdá, Rafael Carmena, Juan F. Ascaso. (2008) Insulin resistance and oxidative stress in familial combined hyperlipidemia. Atherosclerosis 199:2, 384-389
CrossRef65
S. Tsimikas, J. Willeit, M. Knoflach, M. Mayr, G. Egger, M. Notdurfter, J. L. Witztum, C. J. Wiedermann, Q. Xu, S. Kiechl. (2008) Lipoprotein-associated phospholipase A2 activity, ferritin levels, metabolic syndrome, and 10-year cardiovascular and non-cardiovascular mortality: results from the Bruneck study. European Heart Journal 30:1, 107-115
CrossRef66
Burcin Özüyaman, Marijke Grau, Malte Kelm, Marc W. Merx, Petra Kleinbongard. (2008) RBC NOS: regulatory mechanisms and therapeutic aspects. Trends in Molecular Medicine 14:7, 314-322
CrossRef67
Marie-Claire Bélanger, Marc-Édouard Mirault, Eric Dewailly, Line Berthiaume, Pierre Julien. (2008) Environmental contaminants and redox status of coenzyme Q10 and vitamin E in Inuit from Nunavik. Metabolism 57:7, 927-933
CrossRef68
Christian Delles, William H. Miller, Anna F. Dominiczak. (2008) Targeting Reactive Oxygen Species in Hypertension. Antioxidants & Redox Signaling 10:6, 1061-1078
CrossRef69
Kellan E. Ashley, John M. Galla, Stephen J. Nicholls. (2008) Brain Natriuretic Peptides as Biomarkers for Atherosclerosis. Preventive Cardiology 11:3, 172-176
CrossRef70
Ulrich Förstermann. (2008) Oxidative stress in vascular disease: causes, defense mechanisms and potential therapies. Nature Clinical Practice Cardiovascular Medicine 5:6, 338-349
CrossRef71
Marie-Claire Bélanger, Marc-Edouard Mirault, Eric Dewailly, Michel Plante, Line Berthiaume, Micheline Noël, Pierre Julien. (2008) Seasonal mercury exposure and oxidant-antioxidant status of James Bay sport fishermen. Metabolism 57:5, 630-636
CrossRef72
S. E. Espinoza, H. Guo, N. Fedarko, A. DeZern, L. P. Fried, Q.-L. Xue, S. Leng, B. Beamer, J. D. Walston. (2008) Glutathione Peroxidase Enzyme Activity in Aging. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 63:5, 505-509
CrossRef73
Joseph S Meltzer, Vivek K Moitra. (2008) The nutritional and metabolic support of heart failure in the intensive care unit. Current Opinion in Clinical Nutrition and Metabolic Care 11:2, 140-146
CrossRef74
Hung-Yao Ho, Po-Wen Gu, Yi-Li Wang, Jui-Ming Li, Daniel Tsun-Yee Chiu, Mei-Ling Cheng, Chin-Ming Chen. (2008) Oxidative damage markers and antioxidants in patients with acute myocardial infarction and their clinical significance. BioFactors 34:2, 135-145
CrossRef75
Edith Lubos, Joseph Loscalzo, Diane E. Handy. (2007) Homocysteine and Glutathione Peroxidase-1. Antioxidants & Redox Signaling 9:11, 1923-1940
CrossRef76
Fausta Natella, Michela Fidale, Franco Tubaro, Fulvio Ursini, Cristina Scaccini. (2007) Selenium supplementation prevents the increase in atherogenic electronegative LDL (LDL minus) in the postprandial phase. Nutrition, Metabolism and Cardiovascular Diseases 17:9, 649-656
CrossRef77
Tracie L. Miller, Daniela Neri, Jason Extein, Gabriel Somarriba, Nancy Strickman-Stein. (2007) Nutrition in pediatric cardiomyopathy. Progress in Pediatric Cardiology 24:1, 59-71
CrossRef78
Zehra Serdar, Dilek Yeşilbursa, Melahat Dirican, Emre Sarandöl, Akın Serdar. (2007) Sialic acid and oxidizability of lipid and proteins and antioxidant status in patients with coronary artery disease. Cell Biochemistry and Function 25:6, 655-664
CrossRef79
Mitsutoshi Oguri, Kimihiko Kato, Takeshi Hibino, Kiyoshi Yokoi, Tomonori Segawa, Hitoshi Matsuo, Sachiro Watanabe, Yoshinori Nozawa, Toyoaki Murohara, Yoshiji Yamada. (2007) Genetic risk for restenosis after coronary stenting. Atherosclerosis 194:2, e172-e178
CrossRef80
Nisha I Parikh, Ramachandran S Vasan. (2007) Assessing the clinical utility of biomarkers in medicine. Biomarkers in Medicine 1:3, 419-436
CrossRef81
Lutz Schomburg, Cornelia Riese, Kostja Renko, Ulrich Schweizer. (2007) Effect of age on sexually dimorphic selenoprotein expression in mice. Biological Chemistry 388:10, 1035-1041
CrossRef82
John Mercer, Melli Mahmoudi, Martin Bennett. (2007) DNA damage, p53, apoptosis and vascular disease. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 621:1-2, 75-86
CrossRef83
Ruzena Tkacova, Zuzana Kluchova, Pavol Joppa, Darina Petrasova, Angela Molcanyiova. (2007) Systemic inflammation and systemic oxidative stress in patients with acute exacerbations of COPD. Respiratory Medicine 101:8, 1670-1676
CrossRef84
Hong Zhu, Zhuoxiao Cao, Li Zhang, Michael A. Trush, Yunbo Li. (2007) Glutathione and glutathione-linked enzymes in normal human aortic smooth muscle cells: chemical inducibility and protection against reactive oxygen and nitrogen species-induced injury. Molecular and Cellular Biochemistry 301:1-2, 47-59
CrossRef85
Mia Jüllig, Anthony J. Hickey, Martin J. Middleditch, David J. Crossman, Stanley C. Lee, Garth J. S. Cooper. (2007) Characterization of proteomic changes in cardiac mitochondria in streptozotocin-diabetic rats using iTRAQ™ isobaric tags. PROTEOMICS – Clinical Applications 1:6, 565-576
CrossRef86
Mika J. Thomson, Valentina Puntmann, Juan-Carlos Kaski. (2007) Atherosclerosis and Oxidant Stress: The End of the Road for Antioxidant Vitamin Treatment?. Cardiovascular Drugs and Therapy 21:3, 195-210
CrossRef87
Jonica Campolo, Renata De Maria, Raffaele Caruso, Roberto Accinni, Fabio Turazza, Marina Parolini, Elèna Roubina, Benedetta De Chiara, Giuliana Cighetti, Maria Frigerio, Ettore Vitali, Oberdan Parodi. (2007) Blood glutathione as independent marker of lipid peroxidation in heart failure. International Journal of Cardiology 117:1, 45-50
CrossRef88
Rudolf Lampé, Márk Ormos, Sándor Szűcs, Róza Ádány, Edit Szikszay, Robert Póka. (2007) Superoxide anion production of granulocytes in patients with endometrial cancer at presentation and after treatment. European Journal of Obstetrics & Gynecology and Reproductive Biology 131:2, 231-234
CrossRef89
Christine Espinola-Klein, Hans J. Rupprecht, Christoph Bickel, Renate Schnabel, Sabine Genth-Zotz, Micheal Torzewski, Karl Lackner, Thomas Munzel, Stefan Blankenberg. (2007) Glutathione Peroxidase-1 Activity, Atherosclerotic Burden, and Cardiovascular Prognosis. The American Journal of Cardiology 99:6, 808-812
CrossRef90
Benedetta De Chiara, Antonio Mafrici, Jonica Campolo, Gabriella Famoso, Valentina Sedda, Marina Parolini, Giuliana Cighetti, Alessandro Lualdi, Cesare Fiorentini, Oberdan Parodi. (2007) Low plasma glutathione levels after reperfused acute myocardial infarction are associated with late cardiac events. Coronary Artery Disease 18:2, 77-82
CrossRef91
N Abdilla, M C Tormo, M J Fabia, F J Chaves, G Saez, J Redon. (2007) Impact of the components of metabolic syndrome on oxidative stress and enzymatic antioxidant activity in essential hypertension. Journal of Human Hypertension 21:1, 68-75
CrossRef92
Rachel Elsom, Peter Sanderson, John E. Hesketh, Malcolm J. Jackson, Susan J. Fairweather-Tait, Björn Åkesson, Jean Handy, John R. Arthur. (2006) Functional markers of selenium status: UK Food Standards Agency workshop report. British Journal of Nutrition 96:05,
CrossRef93
Christian Delles, Anna F Dominiczak. (2006) Vascular failure or sick vessel syndrome: the cardiovascular continuum is a useful concept for clinical research. Journal of Hypertension 24:11, 2147-2148
CrossRef94
A C White, A M Sousa, J Blumberg, H F Ryan, B L Fanburg, U S Kayyali. (2006) Plasma antioxidants in subjects before hematopoietic stem cell transplantation. Bone Marrow Transplantation 38:7, 513-520
CrossRef95
María-Isabel Covas, Valentina Ruiz-Gutiérrez, Rafael Torre, Anthony Kafatos, Rosa M. Lamuela-Raventós, Jesus Osada, Robert W. Owen, Francesco Visioli. (2006) Minor Components of Olive Oil: Evidence to Date of Health Benefits in Humans. Nutrition Reviews 64, S20-S30
CrossRef96
Mehmet Aslan, Mehmet Horoz, Abdurrahim Kocyigit, Saadet Ozgonül, Hakim Celik, Metin Celik, Ozcan Erel. (2006) Lymphocyte DNA damage and oxidative stress in patients with iron deficiency anemia. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 601:1-2, 144-149
CrossRef97
Matthew A. Roberts, David L. Hare, Sujiva Ratnaike, Francesco L. Ierino. (2006) Cardiovascular Biomarkers in CKD: Pathophysiology and Implications for Clinical Management of Cardiac Disease. American Journal of Kidney Diseases 48:3, 341-360
CrossRef98
Zehra Serdar, Kemal Aslan, Melahat Dirican, Emre Sarandöl, Dilek Yeşilbursa, Akýn Serdar. (2006) Lipid and protein oxidation and antioxidant status in patients with angiographically proven coronary artery disease. Clinical Biochemistry 39:8, 794-803
CrossRef99
Marie-Claire Bélanger, Éric Dewailly, Line Berthiaume, Micheline Noël, Jean Bergeron, Marc-Édouard Mirault, Pierre Julien. (2006) Dietary contaminants and oxidative stress in Inuit of Nunavik. Metabolism 55:8, 989-995
CrossRef100
Roland Gärtner. (2006) Die medizinische Bedeutung von Selen / The clinical relevance of selenium. LaboratoriumsMedizin 30:4, 201-208
CrossRef101
Renu Misra, Sonika Mangi, Sujata Joshi, Suneeta Mittal, Suresh K. Gupta, Ravindra M. Pandey. (2006) LycoRed as an alternative to hormone replacement therapy in lowering serum lipids and oxidative stress markers: A randomized controlled clinical trial. Journal of Obstetrics and Gynaecology Research 32:3, 299-304
CrossRef102
Enzo Emanuele, Colomba Falcone, Angela D’Angelo, Piercarlo Minoretti, Maria P. Buzzi, Marco Bertona, Diego Geroldi. (2006) Association of plasma eotaxin levels with the presence and extent of angiographic coronary artery disease. Atherosclerosis 186:1, 140-145
CrossRef103
Nageswara R. Madamanchi, Igor Tchivilev, Marschall S. Runge. (2006) Genetic markers of oxidative stress and coronary atherosclerosis. Current Atherosclerosis Reports 8:3, 177-183
CrossRef104
Salman Ashfaq, Jerome L. Abramson, Dean P. Jones, Steven D. Rhodes, William S. Weintraub, W. Craig Hooper, Viola Vaccarino, David G. Harrison, Arshed A. Quyyumi. (2006) The Relationship Between Plasma Levels of Oxidized and Reduced Thiols and Early Atherosclerosis in Healthy Adults. Journal of the American College of Cardiology 47:5, 1005-1011
CrossRef105
Michel Lorgeril, Patricia Salen. (2006) Selenium and antioxidant defenses as major mediators in the development of chronic heart failure. Heart Failure Reviews 11:1, 13-17
CrossRef106
Renate Schnabel, Edith Lubos, Hans J. Rupprecht, Christine Espinola-Klein, Christoph Bickel, Karl J. Lackner, François Cambien, Laurence Tiret, Thomas Münzel, Stefan Blankenberg. (2006) B-Type Natriuretic Peptide and the Risk of Cardiovascular Events and Death in Patients With Stable Angina. Journal of the American College of Cardiology 47:3, 552-558
CrossRef107
Emina Colak, Nada Majkic-Singh, Sanja Stankovic, Predrag Djordjevic, Vesna Dimitrijevic-Sreckovic, Katarina Lalic, Nebojsa Lalic. (2006) The effect of hyperglycemia on the values of antioxidative parameters in type 2 diabetic patients with cardiovascular complications. Jugoslovenska medicinska biohemija 25:2, 173-179
CrossRef108
Sven Wassmann, Kerstin Wassmann, Georg Nickenig. (2006) Regulation of antioxidant and oxidant enzymes in vascular cells and implications for vascular disease. Current Hypertension Reports 8:1, 69-78
CrossRef109
Gwo-Hwa Wan, Ken-Kuo Lin, Shu-Chen Tsai, Daniel Tsun-Yee Chiu. (2006) Decreased Glucose-6-PhosphateDehydrogenase (G6PD) Activity and Risk of Senile Cataract in Taiwan. Ophthalmic Epidemiology 13:2, 109-114
CrossRef110
L.A. Lexis, A. Fenning, L. Brown, R.G. Fassett, J.S. Coombes. (2006) Antioxidant Supplementation Enhances Erythrocyte Antioxidant Status and Attenuates Cyclosporine-Induced Vascular Dysfunction. American Journal of Transplantation 6:1, 41-49
CrossRef111
Werner, Nikos, Kosiol, Sonja, Schiegl, Tobias, Ahlers, Patrick, Walenta, Katrin, Link, Andreas, Böhm, Michael, Nickenig, Georg, . (2005) Circulating Endothelial Progenitor Cells and Cardiovascular Outcomes. New England Journal of Medicine 353:10, 999-1007
Full Text112
Colin D. Funk. (2005) Leukotriene modifiers as potential therapeutics for cardiovascular disease. Nature Reviews Drug Discovery 4:8, 664-672
CrossRef113
M. Fitó, M. Cladellas, R. de la Torre, J. Martí, M. Alcántara, M. Pujadas-Bastardes, J. Marrugat, J. Bruguera, M.C. López-Sabater, J. Vila, M.I. Covas. (2005) Antioxidant effect of virgin olive oil in patients with stable coronary heart disease: a randomized, crossover, controlled, clinical trial. Atherosclerosis 181:1, 149-158
CrossRef114
Renate Schnabel, Karl J. Lackner, Hans J. Rupprecht, Christine Espinola-Klein, Michael Torzewski, Edith Lubos, Christoph Bickel, François Cambien, Laurence Tiret, Thomas Münzel, Stefan Blankenberg. (2005) Glutathione Peroxidase-1 and Homocysteine for Cardiovascular Risk Prediction. Journal of the American College of Cardiology 45:10, 1631-1637
CrossRef115
Emel Altekin, Canan Çoker, Ali Rıza Şişman, Banu Önvural, Filiz Kuralay, Önder Kırımlı. (2005) The relationship between trace elements and cardiac markers in acute coronary syndromes. Journal of Trace Elements in Medicine and Biology 18:3, 235-242
CrossRef116
Guilherme H. M. Oliveira. (2005) Novel serologic markers of cardiovascular risk. Current Atherosclerosis Reports 7:2, 148-154
CrossRef117
T. Szelestei, S. Bahring, Z. Wagner, A. Aydin, G. A. Molnar, B. Kocsis, J. Nagy, I. Wittmann. (2005) Serum levels of l-arginine analogues and glutathione peroxidase and catalase gene variants in Type 2 diabetes mellitus patients. Diabetic Medicine 22:3, 356-357
CrossRef118
I. J. Kullo, C. M. Ballantyne. (2005) Conditional Risk Factors for Atherosclerosis. Mayo Clinic Proceedings 80:2, 219-230
CrossRef119
José A. Páramo, Ramón Lecumberri, Josune Orbe. (2005) Trombosis arterial y polimorfismos genéticos: demasiados actores, escenario complejo. Medicina Clínica 124:2, 69-74
CrossRef120
Mei-ling Cheng, Hung-yao Ho, Hsiu-chuan Tseng, Chien-Hong Lee, Lee-yung Shih, Daniel Tsun-yee Chiu. (2005) Antioxidant deficit and enhanced susceptibility to oxidative damage in individuals with different forms of α -thalassaemia. British Journal of Haematology 128:1, 119-127
CrossRef121
Jagat Narula, H. William Strauss. (2005) Imaging of unstable atherosclerotic lesions. European Journal of Nuclear Medicine and Molecular Imaging 32:1, 1-5
CrossRef122
Barbara Voetsch, Richard C. Jin, Joseph Loscalzo. (2004) Nitric oxide insufficiency and atherothrombosis. Histochemistry and Cell Biology 122:4, 353-367
CrossRef123
Jesse Adams. (2004) Markers to define ischemia: Are they ready for prime time use in patients with acute coronary syndromes?. Current Cardiology Reports 6:4, 253-258
CrossRef124
Fong-Fong Chu, R.Steven Esworthy, James H. Doroshow. (2004) Role of Se-dependent glutathione peroxidases in gastrointestinal inflammation and cancer. Free Radical Biology and Medicine 36:12, 1481-1495
CrossRef125
Barbara Voetsch, Joseph Loscalzo. (2004) Genetics of thrombophilia: impact on atherogenesis. Current Opinion in Lipidology 15:2, 129-143
CrossRef126
Ren?? L Chiol??ro, Kenneth Kudsk. (2004) Current concepts in nutrition delivery in critically ill patients: route, insulin, and economics. Current Opinion in Clinical Nutrition and Metabolic Care 7:2, 157-159
CrossRef127
Doron Aronson. (2004) Inflammatory markers: linking unstable plaques to coronary event, an interventional perspective. Acute Cardiac Care 6:3-4, 110-118
CrossRef128
Manolio, Teri, . (2003) Novel Risk Markers and Clinical Practice. New England Journal of Medicine 349:17, 1587-1589
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