8-hydroxy-2--deoxyguanosine and Coronary-Artery-Disease

Exposure to fine particulate matter increases the risk of cardiovascular morbidity and mortality. Few studies have tested the beneficial effect of indoor air filtration intervention in patients with cardiovascular disease. The aim of this study is to investigate the effect of air filtration on mitigating cardiovascular health in patients with coronary artery disease. This randomized, double-blind, crossover study is conducted with 38 coronary artery disease patients. The intervention consists of the following three periods: two-week active and sham air filtration interventions, with a two-week washout period. The indoor PM

Topics: 8-Hydroxy-2'-Deoxyguanosine; Air Filters; Air Pollutants; Air Pollution, Indoor; Baroreflex; Biomarkers; Cardiovascular Diseases; Coronary Artery Disease; Cross-Over Studies; Humans; Oxidative Stress; Particulate Matter

To reduce the increase of oxidative stress and the upregulation of CD40L during stenting procedure using ascorbic acid infusion.. CD40L upregulation occurring after coronary percutaneous coronary intervention predicts vascular events but the underlying mechanism is still unclear.. Fifty-six patients undergoing elective coronary stenting were randomly allocated to intravenous infusion of the antioxidant ascorbic acid or placebo. Platelet CD40L and plasma levels of soluble CD40L and of 8-hydroxy-2'-deoxyguanosine, a marker of oxidative stress, were measured before and after coronary stenting. In vitro study was also done to measure reactive oxidant species and CD40L expression in platelets exposed to anoxia-reoxygenation.. Placebo-treated patients showed a significant increase of platelet CD40L, soluble CD40L and 8-hydroxy-2'-deoxyguanosine compared to baseline values. Patients given ascorbic acid showed no change of soluble CD40L and platelet CD40L but a significant decrease of 8-hydroxy-2'-deoxyguanosine. After 60 and 120 min, soluble CD40L, platelet CD40L and 8-hydroxy-2'-deoxyguanosine were significantly lower in the ascorbic acid-treated group compared to the placebo-treated one. A significant correlation between platelet CD40L and soluble CD40L and between soluble CD40L and 8-hydroxy-2'-deoxyguanosine was observed. Platelets, in vitro exposed to anoxia-reoxygenation, had a burst of ROS and an upregulation of CD40L that were inhibited by ascorbic acid or apocynin, an inhibitor of NADPH oxidase.. This study shows that in patients undergoing coronary stenting CD40L is upregulated with a mechanism which is likely mediated by oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acetophenones; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Antioxidants; Ascorbic Acid; Biomarkers; Blood Platelets; CD40 Ligand; Coronary Artery Disease; Deoxyguanosine; Enzyme Inhibitors; Female; Flow Cytometry; Humans; Infusions, Intravenous; Italy; Linear Models; Male; Middle Aged; NADPH Oxidases; Oxidative Stress; Pilot Projects; Placebos; Prospective Studies; Reactive Oxygen Species; Stents; Time Factors; Treatment Outcome; Up-Regulation

Little is known about whether mitochondria 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of mitochondrial DNA (mtDNA) oxidative damage, contributes to the development of coronary artery disease (CAD) in diabetic patients. Here, we explored the associations of mtDNA 8-OHdG in leukocytes with obstructive CAD, coronary stenosis severity, cardiovascular biomarkers, and 1-year adverse outcomes after coronary revascularization in patients with type 2 diabetes mellitus (T2DM).. In a total of 1920 consecutive patients with T2DM who underwent coronary angiography due to symptoms of angina or angina equivalents, the presence of obstructive CAD, the number of diseased vessels with ≥ 50% stenosis, and modified Gensini score were cross-sectionally evaluated; the level of mtDNA 8-OHdG was quantified by quantitative PCR. Then, 701 of 1920 diabetic patients who further received coronary revascularization completed 1-year prospective follow-up to document major adverse cardiovascular and cerebral events (MACCEs). In vitro experiments were also performed to observe the effects of mtDNA oxidative damage in high glucose-cultured human umbilical vein endothelial cells (HUVECs).. Cross-sectionally, greater mtDNA 8-OHdG was associated with increased odds of obstructive CAD (odds ratio [OR] 1.38, 95% CI confidence interval 1.24-1.52), higher degree of coronary stenosis (number of diseased vessels: OR 1.29, 95% CI 1.19-1.41; modified Gensini scores: OR 1.28, 95% CI 1.18-1.39), and higher levels of C-reactive protein (β 0.18, 95% CI 0.06-0.31) after adjusting for confounders. Sensitivity analyses using propensity score matching yielded similar results. Stratification by smoking status showed that the association between mtDNA 8-OHdG and obstructive CAD was most evident in current smokers (P. Greater mtDNA 8-OHdG in leukocytes may serve as an independent risk factor for CAD in patients with T2DM.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; Cells, Cultured; China; Coronary Artery Disease; Coronary Stenosis; Cross-Sectional Studies; Diabetes Mellitus, Type 2; DNA Damage; DNA, Mitochondrial; Female; Human Umbilical Vein Endothelial Cells; Humans; Leukocytes; Male; Middle Aged; Myocardial Revascularization; Oxidative Stress; Prospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Time Factors; Treatment Outcome

Oxidative stress (OS) is related to vascular inflammation possibly, contributing to the development of coronary ectasia (CE). Base excision repair (BER) and nucleotide excision repair are the main DNA repair pathways that can help to remove 8-hydroxydeoxyguanine (8-OHdG), a marker of OS. Human 8-oxoguanine DNA glycosylase 1 (hOGG1) is a key enzyme of the BER pathway and catalyzes the removal of 8-OHdG. The aim of our study was to investigate the association between hOGG1 Ser326Cys gene polymorphism and CE in a Chinese population. Five-hundred forty-seven patients who underwent diagnostic coronary angiography in a tertiary medical center were recruited. The angiographic definition of CE is the diameter of the ectatic segment being more than 1.5 times larger compared with an adjacent healthy reference segment. The gene polymorphisms were analyzed by polymerase chain reaction. The urine 8OHdG concentration was measured using a commercial ELISA kit. The distribution of hOGG1 Ser326Cys genotypes was significantly different between CE and non-CE groups (p = 0.033). The odds ratio of CE development for the Ser to the Cys variant was 1.55 (95% confidence interval (CI), 1.04-2.31, p = 0.033). Both univariate and logistic regression analysis showed a significant association of hOGG1 Ser326Cys polymorphism in the dominant model with CE development (p = 0.009 and 0.011, respectively). Urine 8-OHdG levels were significantly higher in subjects carrying the hOGG1 Ser variant than in those with the Cys/Cys genotype (p < 0.03). In conclusion, our study suggests that the hOGG1 Ser326Cys gene variant might play a role in susceptibility to the development of CE.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Case-Control Studies; China; Coronary Artery Disease; Deoxyguanosine; Dilatation, Pathologic; DNA Glycosylases; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Mutation, Missense; Polymorphism, Single Nucleotide; Radiography

In view of growing body of evidence favouring the association of aberrations in one-carbon metabolism and oxidative stress in the aetiology of coronary artery disease (CAD), we investigated the risk associated with polymorphisms regulating the folate uptake and transport such as the glutamate carboxypeptidase II (GCPII) C1561T, reduced folate carrier 1 (RFC1) G80A and cytosolic serine hydroxymethyltransferase (cSHMT) C1420T. We further evaluated the impact of seven putatively functional polymorphisms of this pathway on oxidative stress markers. Genotyping was performed on 288 CAD cases and 266 healthy controls along with the dietary folate assessment. GCPII C1561T polymorphism was found to be an independent risk factor (OR 2.71, 95% CI 1.47-4.98) for CAD, whereas cSHMT C1420T conferred protection (OR 0.51, 95% CI 0.37-0.70). Oxidative stress markers like the plasma levels of malondialdehyde, protein carbonyls and 8-oxo-deoxyguanosine were significantly increased and total glutathione was significantly decreased in CAD cases. Elevated oxidative stress was observed in subjects carrying GCPII 1561T and MTRR 66A-variant alleles and low oxidative stress was observed in the subjects carrying cSHMT 1420T and TYMS 5'-UTR 2R allele. GCPII C1561T, MTHFR C677T and MTRR A66G polymorphisms were observed to influence the homocysteine levels (P < 0.05). SHMT and TYMS variants were found to decrease oxidative stress by increasing the folate pool (r = 0.38, P = 0.003) and also by increasing the antioxidant status (r = 0.28, P = 0.03). Influence of dietary folate status was not observed. Overall, this study revealed elevated oxidative stress that was associated with the aberrations in one-carbon metabolism which could possibly influence the CAD risk.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Carbon; Coronary Artery Disease; Deoxyguanosine; Female; Glutathione; Humans; Male; Malondialdehyde; Oxidative Stress; Polymorphism, Genetic; Protein Carbonylation

The correlation of coronary artery disease (CAD) with pro-oxidant/antioxidant balance and oxidative DNA damage was investigated. Seventy-seven patients with CAD and 44 healthy individuals as control were included in this study. The comparative ratios of ubiquinol-10/ubiquinone-10, 8-hydroxy-2(')-deoxyguanosine/deoxyguanosine and the level of MDA measured by HPLC and the activities of GPX and SOD by colorimetric approach in blood samples obtained from patients with CAD were unraveled.8-OHdG/dG ratios, serum MDA level and GPX activity were found significantly elevated level in serum of CAD patients compared to control group. The SOD activity was observed in stable levels in CAD patients. Ubiquinol-10/ubiquinone-10 ratio was significantly lower in patients with CAD than the controls. The positive correlation was observed between 8-OHdG/dG ratios in both MDA levels and GPX activity, while the significant negative correlation was seemed between the ratio of 8-OHdG/dG and ubiquinol-10/ubiquinone-10 as well as MDA levels and ubiquinol-10/ubiquinone-10 ratio. We conclude that, both the disruption of pro-oxidant/antioxidant balance and oxidative stress in DNA may play an important role in the pathogenesis of coronary artery disease.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Case-Control Studies; Chromatography, High Pressure Liquid; Coronary Artery Disease; Deoxyguanosine; DNA Damage; Female; Glutathione Peroxidase; Humans; Male; Middle Aged; Oxidative Stress; Superoxide Dismutase; Ubiquinone

Oxidative stress is involved in the pathogenesis of atherosclerosis. 8-Hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative product of DNA, is a sensitive biomarker to reflect oxidative stress status in vivo. However, the circulating 8-OHdG levels in patients with coronary artery disease (CAD) have not yet been elucidated. The purpose of this study is to investigate whether serum 8-OHdG levels are associated with the presence and severity of CAD.. We measured serum 8-OHdG levels by enzyme-linked immunosorbent assay in 127 patients with suspected CAD who underwent coronary angiography. The severity of CAD was assessed by the number of diseased vessels and Gensini score.. The serum 8-OHdG levels in patients with CAD were significantly higher than those in patients with normal coronary arteries [median (interquartile range), 0.41 (0.30-0.57) ng/ml versus 0.32 (0.25-0.43) ng/ml, P = 0.001]. Log (8-OHdG) levels increased with the number of diseased vessels (P = 0.002) and significantly correlated with Gensini score (r = 0.379, P = 0.001). The multivariable logistic regression analysis showed that serum 8-OHdG was independently associated with the presence of CAD (odds ratio, 1.318; P = 0.027).. In conclusion, the serum 8-OHdG levels are increased in patients with CAD and are associated with the severity of coronary artery stenosis. 8-OHdG might serve as an independent factor for predicting CAD.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; Coronary Angiography; Coronary Artery Disease; Deoxyguanosine; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Oxidative Stress

It is known that n-3 polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid and eicosapentaenoic acid, are rapidly oxidized in vitro. Nvarepsilon-(propanoyl)lysine (propionyllysine, or PRL) is formed from the reaction of the oxidized products of n-3 PUFAs and lysine. To evaluate the oxidized n-3 PUFA-derived protein modifications in vivo, we have developed detection methods using a novel monoclonal antibody against PRL as well as liquid chromatography-mass spectrometry (LC/MS/MS). The antibody obtained specifically recognized PRL. A strong positive staining in atherosclerotic lesions of hypercholesterolemic rabbits was observed. We have also simultaneously identified and quantified both urinary PRL and urinary Nvarepsilon-(hexanoyl)lysine, using LC/MS/MS using isotope dilution methods. The level of urinary PRL (21.6+/-10.6 micromol/mol of creatinine) significantly correlated with the other oxidative stress markers, 8-oxo-deoxyguanosine, dityrosine, and isoprostanes. The increase in the excretion of amide adducts into the urine of diabetic patients was also confirmed compared to healthy subjects. These results suggest that PRL may be good marker for n-3 PUFA-derived oxidative stress in vivo.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antibodies, Monoclonal; Aorta; Biomarkers; Coronary Artery Disease; Deoxyguanosine; Diabetes Insipidus; Dinoprost; Fatty Acids, Unsaturated; Humans; Hypercholesterolemia; Immunochemistry; Lysine; Mass Spectrometry; Oxidation-Reduction; Oxidative Stress; Propionates; Rabbits

Various oxidative stress markers have been measured to evaluate the status of heart failure (HF). However, the relationships between these markers and the aetiology of HF have not been fully investigated. This study compared 8-hydroxy-2'-deoxyguanosine (8-OHdG) and biopyrrins levels in patients with ischemic and non-ischemic HF. Study subjects were divided into a coronary artery disease (CAD) group (n=70), a non-CAD group (n=61) and a control group (n=33). In the CAD group, 8-OHdG and biopyrrins levels increased with the severity of the New York Heart Association (NYHA) functional class and log BNP levels correlated with 8-OHdG and biopyrrins levels. However, non-CAD patients with NYHA class III/IV had significantly lower 8-OHdG levels than CAD patients with NYHA class III/IV and the levels did not correlate with log BNP levels. In the CAD group, 8-OHdG levels reflected the severity of atherosclerosis. These results indicate that the properties of oxidative stress markers should be carefully taken into consideration for the assessment of HF status.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Bilirubin; Biomarkers; Coronary Artery Disease; Deoxyguanosine; Female; Heart Failure; Humans; Male; Middle Aged; Oxidative Stress

The common C242T polymorphism in the gene for the p22phox subunit of NADPH oxidase has been reported to be negatively associated with oxidative stress, but whether it confers prognostic information is not yet clear.. The incidence of major adverse cardiovascular events (MACE) were determined in 237 patients with coronary stenosis during a median follow-up of 7.8 years. The p22phox genotypes were evaluated in 213 patients (89.9%) by polymerase chain reaction and RsaI. digestion. Plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative stress, were also measured. In the univariate analysis, patients with CT/TT genotypes showed reduced recurrence of cardiovascular deaths, nonfatal MI, and revascularization procedures compared with homozygous carriers of the C allele. After controlling for confounders, a significantly lower risk of new revascularization procedures (HR=0.31, 95% CI 0.12 to 0.70; P=0.014) remained associated with the T allele. The Kaplan-Meier analysis showed a longer survival free from fatal and nonfatal MI in carriers of T allele (P<0.001). The presence of the 242T allele was associated with significantly reduced plasma concentrations of 8-OHdG.. The 242T allele was a predictor of lower risk of recurrence of cardiovascular events in high-risk patients and was associated with reduced systemic oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Alleles; Biomarkers; Cohort Studies; Coronary Artery Disease; Deoxyguanosine; Female; Follow-Up Studies; Genotype; Humans; Male; Middle Aged; NADPH Oxidases; Oxidative Stress; Polymorphism, Single Nucleotide; Prognosis; Recurrence; Risk Factors

Folic acid deficiency increases stroke risk. In the present study, we examined whether folic acid deficiency enhances neuronal damage and gliosis via oxidative stress in the gerbil hippocampus after transient forebrain ischemia. Animals were exposed to a folic acid-deficient diet (FAD) for 3 months and then subjected to occlusion of both common carotid arteries for 5 min. Exposure to an FAD increased plasma homocysteine levels by five- to eightfold compared with those of animals fed with a control diet (CD). In CD-treated animals, most neurons were dead in the hippocampal CA1 region 4 days after ischemia/reperfusion, whereas, in FAD-treated animals, this occurred 3 days after ischemia/reperfusion. Immunostaining for 8-hydroxy-2'-deoxyguanosine (8-OHdG) was performed to examine DNA damage in CA1 neurons in both groups after ischemia, and it was found that 8-OHdG immunoreactivity in both FAD and CD groups peaked at 12 hr after reperfusion, although the immunoreactivity in the FAD group was much greater than that in the CD group. Platelet endothelial cell adhesion molecule-1 (PECAM-1; a final mediator of neutrophil transendothelial migration) immunoreactivity in both groups increased with time after ischemia/reperfusion: Its immunoreactivity in the FAD group was much higher than that in the CD group 3 days after ischemia/reperfusion. In addition, reactive gliosis in the ischemic CA1 region increased with time after ischemia in both groups, but astrocytosis and microgliosis in the FAD group were more severe than in the CD group at all times after ischemia. Our results suggest that folic acid deficiency enhances neuronal damage induced by ischemia.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Cell Death; Coronary Artery Disease; Deoxyguanosine; Disease Models, Animal; DNA Damage; Folic Acid Deficiency; Gerbillinae; Immunohistochemistry; In Situ Nick-End Labeling; Ischemic Attack, Transient; Male; Neurons; Platelet Endothelial Cell Adhesion Molecule-1; Prosencephalon

Activation of the lectin-like oxLDL receptor (LOX-1) promotes atherosclerosis. Oxidized LDL (oxLDL) increases production of reactive oxygen species (ROS) and leads to the development of endothelial dysfunction. The molecular causes for oxLDL to induce oxidative DNA damage and metabolic dysfunction remain uncertain. Here we report treatment of cultured human coronary arterial endothelial cells (HCAEC) with oxLDL to cause oxidative DNA damage as determined by a 3-fold increase in 8-OH-desoxyguanosine adduct formation and a 4-fold induction of the growth arrest and DNA damage-inducible transcripts GADD45 and GADD153. Oxidative stress resulted in activation of Oct-1, a transcriptional repressor of various vascular cytochrome P450 (CYP) monooxygenases. Activation of Oct-1 was protein kinase C (PKC)-mediated. Binding of Oct-1 to promoter sequences of CYP monooxygenases was increased upon treatment of HCAEC with oxLDL. This resulted in repressed production of endothelium-derived hyperpolarization factor 11,12-epoxyeicosatrieonic acid. Small interference RNA-mediated functional knockdown of Oct-1 prevented oxLDL-mediated silencing of CYP expression. Inhibition of LOX-1 attenuated oxLDL-mediated endothelial DNA damage, Oct-1/DNA binding, and reversed impaired production of EDHF. Taken collectively, oxLDL induced oxidative DNA damage and activation of Oct-1 to result in metabolic dysfunction of coronary arterial endothelium.

Topics: 8-Hydroxy-2'-Deoxyguanosine; 8,11,14-Eicosatrienoic Acid; Biological Factors; Cell Cycle Proteins; Cells, Cultured; Coronary Artery Disease; Coronary Vessels; Cytochrome P-450 Enzyme System; Deoxyguanosine; DNA Adducts; DNA Damage; Endothelial Cells; Endothelium, Vascular; Humans; Lipoproteins, LDL; Nuclear Proteins; Octamer Transcription Factor-1; Oxidative Stress; Protein Kinase C; Reactive Oxygen Species; Repressor Proteins; Response Elements; RNA, Small Interfering; Scavenger Receptors, Class E; Transcription Factor CHOP

Exposure to a large number of environmental toxins can induce damage to DNA and may play an important role in the pathophysiological processes of atherosclerosis. To examine the effect of some specific environmental conditions that predispose to sudden coronary atherosclerotic death on the level of 8-OHdG, urine samples were collected from cases of certain occupations and polluted regions that showed a high prevalence of premature deaths. The samples were then analyzed for 8-OHdG. Analysis of 108 cases and 45 controls showed a significant high level of 8-OHdG in relation to occupations, habits, residency and work shift. The mean +/- standard deviation (M +/- SD) for the control group was 4.5 +/- 2.3 ng 8-OHdG/mg creatinine (n = 45), compared to 9.1 +/- 3.1 ng/mg in taxi drivers (n = 9), 10 +/- 5.5 ng/mg in chemical factory workers (n = 16), 12.0 +/- 8.9 ng/mg in paint workers (n = 9), 14.6 +/- 11.1 ng/mg in gasoline station workers (n = 15), 15 +/- 6.1 ng/mg in cement factory workers (n = 12), 16.4 +/- 3.2 ng/mg in city center inhabitants (n = 18) and 18.6 +/- 3.2 ng/mg in smokers (n = 15). These conditions at least in the pilot study done by the author, showed some form of precipitation of sudden atherosclerotic coronary death. This work proved that the recently used 8-OHdG DNA damage biomarker may be an important marker of environmental conditions that are expected to have a serious long-term impact on the cardiovascular system.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Coronary Artery Disease; Death, Sudden, Cardiac; Deoxyguanosine; DNA Damage; Environmental Exposure; Forecasting; Humans; Jordan; Middle Aged; Occupational Exposure; Occupational Health; Pilot Projects; Prevalence