8-hydroxy-2--deoxyguanosine and Cardiovascular-Diseases

8-Hydroxy-2-deoxyguanosine (8-OHdG) is generated after the repair of ROS-mediated DNA damages and, thus, is one of the most widely recognized biomarkers of oxidative damage of DNA because guanosine is the most oxidized among the DNA nucleobases. In several pathological conditions, high urinary levels of oxidized DNA-derived metabolites have been reported (e.g., cancer, atherosclerosis, hypertension, and diabetes).. Even if published studies have shown that DNA damage is significantly associated with the development of atherosclerosis, the exact role of this damage in the onset and progression of this pathology is not fully understood, and the association of oxidative damage to DNA with cardiovascular disease (CVD) still needs to be more extensively investigated. We performed a meta-analysis of the literature to investigate the association among 8-OHdG levels and CVD.. Fourteen studies (810 CVD patients and 1106 controls) were included in the analysis. We found that CVD patients showed higher 8-OHdG levels than controls (SMD: 1.04, 95%CI: 0.61, 1.47, p < 0.001, I(2) = 94%, p < 0.001). The difference was confirmed both in studies in which 8-OHdG levels were assessed in urine (MD: 4.43, 95%CI: 1.71, 7.15, p = 0.001) and in blood samples (MD: 1.42, 95%CI: 0.64, 2.21, p = 0.0004). Meta-regression models showed that age, hypertension, and male gender significantly impacted on the difference in 8-OHdG levels among CVD patients and controls.. 8-OHdG levels are higher in patients with CVD than in controls. However, larger prospective studies are needed to test 8-OHdG as a predictor of CVD.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Deoxyguanosine; Humans; Oxidation-Reduction; Oxidative Stress; Prognosis; Publication Bias; Regression Analysis

Oxidative stress due to an excess of reactive oxygen species (ROS) may play a role in the development and progression of cardiovascular disease (CVD). 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a marker of oxidative DNA damage caused by ROS. This review aimed to assess the association between 8-OHdG and CVD by reviewing the literature. Studies in human subjects using either plasma or urine to determine 8-OHdG concentrations were surveyed. Eighteen relevant studies were found, of which 13 were case-control studies and five had a prospective design. Without exception, the case-control studies showed significant positive associations between 8-OHdG and CVD. In agreement, two prospective studies showed a significant association of 8-OHdG and heart failure. Furthermore, two prospective studies found a significant association between 8-OHdG and stroke, and finally, one prospective study showed a borderline significant (p = 0.08) association between coronary artery disease (CAD) patients developing a cardiac event and 8-OHdG concentrations. In conclusion, high levels of 8-OHdG in blood and urine are associated with atherosclerosis and heart failure, but further large prospective studies are needed to investigate 8-OHdG as a predictor for cardiovascular diseases.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Cardiovascular Diseases; Clinical Trials as Topic; Deoxyguanosine; DNA Damage; Humans; Oxidative Stress; Reactive Oxygen Species

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

Statins are thought to have anti-atherogenic effects beyond cholesterol lowering. One such mechanism may involve reduction of oxidative stress. The aim of our study was to investigate and to compare the oxidative stress lowering capacity of atorvastatin with that of simvastatin in patients at high risk for cardiovascular disease using conventional markers and sensitive markers measured by highly specific techniques such as liquid chromatography tandem mass spectrometry.. We included 30 statin-naive patients with diabetes mellitus, and/or obesity, and/or hypertension (12 male, 18 female, mean age 44.8±11.1 years), and randomised them to receive either atorvastatin 10 mg or simvastatin 40 mg daily to obtain an equimolar cholesterol reduction. Blood and urine samples were obtained at baseline and at 1, 6 and 12 weeks.. Low-density lipoprotein (LDL) cholesterol and coenzyme Q10 decreased significantly in both groups. Simvastatin caused a faster initial LDL cholesterol lowering than atorvastatin (p=0.01), but the overall effect after 12 weeks of atorvastatin and simvastatin was similar. Plasma myeloperoxidase and malondialdehyde did not change during the study period in the two groups. Urinary F2-isoprostanes decreased gradually and significantly in the atorvastatin group but not in the simvastatin group, but the between-group difference was not significant. Urinary 8-hydroxy-2-deoxyguanosine did not change in the two groups.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Atorvastatin; Cardiovascular Diseases; Cholesterol, LDL; Deoxyguanosine; F2-Isoprostanes; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Peroxidase; Pyrroles; Simvastatin; Ubiquinone

Metabolic syndrome (MetS), in which a non-classic feature is an increase in systemic oxidative biomarkers, presents a high risk of diabetes and cardiovascular disease (CVD). Adherence to the Mediterranean Diet (MedDiet) is associated with a reduced risk of MetS. However, the effect of the MedDiet on biomarkers for oxidative damage has not been assessed in MetS individuals. We have investigated the effect of the MedDiet on systemic oxidative biomarkers in MetS individuals.. Randomized, controlled, parallel clinical trial in which 110 female with MetS, aged 55-80, were recruited into a large trial (PREDIMED Study) to test the efficacy of the traditional MedDiet on the primary prevention of CVD. Participants were assigned to a low-fat diet or two traditional MedDiets (MedDiet + virgin olive oil or MedDiet + nuts). Both MedDiet group participants received nutritional education and either free extra virgin olive oil for all the family (1 L/week), or free nuts (30 g/day). Diets were ad libitum. Changes in urine levels of F2-Isoprostane (F2-IP) and the DNA damage base 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) were evaluated at 1-year trial.. After 1-year urinary F2-IP decreased in all groups, the decrease in MedDiet groups reaching a borderline significance versus that of the Control group. Urinary 8-oxo-dG was also reduced in all groups, with a higher decrease in both MedDiet groups versus the Control one (P < 0.001).. MedDiet reduces oxidative damage to lipids and DNA in MetS individuals. Data from this study provide evidence to recommend the traditional MedDiet as a useful tool in the MetS management.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Deoxyguanosine; Diet, Fat-Restricted; Diet, Mediterranean; DNA Damage; F2-Isoprostanes; Female; Humans; Lipid Metabolism; Metabolic Syndrome; Middle Aged; Nuts; Olive Oil; Oxidative Stress; Plant Oils; Risk Factors; Risk Reduction Behavior

While biomarkers have been proposed to identify individuals at risk for radiation-induced cardiovascular disease (RICVD), little is known about long-term associations with cardiac events. We examined associations of biomarkers of oxidative stress (myeloperoxidase, growth differentiation factor-15, 8-hydroxy-2'-deoxyguanosine [8-OH-dG], placental growth factor), cardiac injury (troponin I, cystatin-C), inflammation (interleukin-6, C-reactive protein), and myocardial fibrosis (transforming growth factor-ß) with long-term RICVD in breast cancer (BC) survivors. We conducted a nested case-control study within the Women's Health Initiative of postmenopausal women with incident BC stages I-III, who received radiation and had pre- and post-BC diagnosis serum samples. Cases (n = 55) were defined as developing incident, physician-adjudicated myocardial infarction, coronary heart disease death, other CVD death, heart failure, or stroke after BC. Cases were matched to three controls (n = 158). After adjustment, a higher 8-OH-dG ratio was significantly associated with an elevated long-term risk of RICVD, suggesting oxidative DNA damage may be a putative pathway for RICVD.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Breast Neoplasms; Cardiovascular Diseases; Case-Control Studies; Female; Humans; Myocardial Infarction; Oxidative Stress; Placenta Growth Factor; Risk Factors

Acrylamide (ACR) exposure and consequent health hazards are alarming public health issues that attract worldwide concern. The World Health Organization urges more researches into health hazards from ACR exposure. However, whether and how ACR exposure increases cardiovascular risk remain unclear, and we sought to address these issues in this prospective cohort study conducted on 3024 general adults with 3-year follow-up (N = 871 at follow-up). Individual urinary ACR metabolites (N-Acetyl-S-(2-carbamoylethyl)-L-cysteine [AAMA] and N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine [GAMA]) as credible biomarkers of ACR exposure were detected to assess their cross-sectional and longitudinal relationships with 10-year cardiovascular disease (CVD) risk, a well measure of overall cardiovascular risk. Besides, biomarkers of oxidative stress (urinary 8-hydroxy-deoxyguanosine [8-OHdG] and 8-iso-prostaglandin-F2α [8-iso-PGF2α]) and inflammation (circulating mean platelet volume [MPV] and plasma C-reactive protein [CRP]) as well as plasma transforming growth factor-β1 (TGF-β1) were measured to assess their mediating/mechanistic roles in the relationships of ACR metabolites with 10-year CVD risk. We found AAMA, GAMA, and ΣUAAM (AAMA + GAMA) were cross-sectionally and longitudinally related to increased 10-year CVD risk with odds ratios (95% confidence intervals [CIs]) of 1.32 (1.04, 1.70), 1.81 (1.36, 2.40), and 1.40 (1.07, 1.82), respectively, and risk ratios (95% CIs) of 1.99 (1.10, 3.60), 2.48 (1.27, 4.86), and 2.13 (1.15, 3.94), respectively. Furthermore, 8-OHdG, 8-iso-PGF2α, MPV, CRP, and TGF-β1 were found to significantly mediate 8.06-48.92% of the ACR metabolites-associated 10-year CVD risk increment. In summary, daily ACR exposure of general adults was cross-sectionally and longitudinally associated with increased cardiovascular risk, which was partly mediated by oxidative stress, inflammation, and TGF-β1, suggesting for the first time that ACR exposure may well increase cardiovascular risk of general adult population partly by mechanisms of inducing oxidative stress, inflammation, and TGF-β1. Our findings have important public health implications that provide potent epidemiological evidence and vital mechanistic insight into cardiovascular risk increment from ACR exposure.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acetylcysteine; Acrylamide; Adult; Biomarkers; Cardiovascular Diseases; Cross-Sectional Studies; Heart Disease Risk Factors; Humans; Inflammation; Oxidative Stress; Prospective Studies; Risk Factors; Transforming Growth Factor beta1

Enhanced oxidative stress-generated nucleoside damage may contribute to the increased cardiovascular disease mortality in patients with bipolar disorder (BD) but the association has never been investigated. We investigated the associations between oxidative stress-generated damage to DNA (8-oxodG) and RNA (8-oxoGuo), respectively, and three measures reflecting cardiovascular risk; namely, the Framingham 30-year risk score of cardiovascular diseases, the metabolic syndrome, and the insulin resistance index in 360 patients newly diagnosed with BD, 102 of their unaffected relatives (UR) and 197 healthy control individuals (HC). In sex- and age-adjusted models, the 30-year cardiovascular risk score increased by 20.8% (CI = 7.4-35.9%, p = 0.002) for every one nM/mM creatinine increase in 8-oxoGuo and by 15.6% (95% CI = 5.8-26.4%, p = 0.001) for every one nM/mM creatinine increase in 8-oxodG, respectively. Further, insulin resistance index increased by 24.1% (95% CI = 6.7-43%, p = 0.005) when 8-oxoGuo increased one nM/mM creatinine. The associations between cardiovascular measures and oxidative nucleoside damage were more pronounced in patients with BD compared with UR, and HC. Metabolic syndrome was not associated with nucleoside damage. Overall, higher oxidative stress-generated nucleoside damage was associated with a higher cardiovascular risk score and a higher degree of insulin resistance index, and having BD impacted the associations. Further, within patients, treatment with psychotropics seemed to enhance the associations between 30-year CVD risk score and insulin resistance index, respectively, and oxidatively stress-generated nucleoside damage. Our findings support enhanced oxidative stress-generated nucleoside damage as a putative pathophysiological mechanism that may mediate the higher cardiovascular risk observed in patients with BD already at the time of diagnosis.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Bipolar Disorder; Cardiovascular Diseases; Case-Control Studies; Creatinine; Heart Disease Risk Factors; Humans; Insulin Resistance; Nucleosides; Oxidative Stress; Risk Factors

Heavy metals (HMs) have a very significant clinical role in the pathogenesis, progression and management of cardiovascular diseases (CVDs). The prevalence of CVDs was reported to be higher in critically environmentally HM-polluted (EHMP) steel industrial town Mandi-Gobindgarh (India) for the last more than a decade. To ascertain the role of HMs in the onset of CVDs, the present study was chosen to investigate HMs content in myocardial infarction (MI) patients from EHMP steel industrial town Mandi-Gobindgarh. Total of 110 MI patients along with number- and age-matched healthy volunteers were recruited in the present investigation. The CVDs risk factors estimated in MI patients were overweight (higher body mass index), hypertension (higher systolic and diastolic blood pressures), dyslipidaemia (higher serum cholesterol, triglycerides and lower HDL cholesterol), inflammation (higher-serum C reactive protein and aldosterone) and elevated oxidative stress (higher urinary 8-hydroxydeoxyguanosine). An imbalance of serum electrolyte concentrations including Na (hypernatremia), Ca (hypercalcaemia) and K (hypokalaemia) was also observed in MI patients in which CVDs risk factors were found to correlate positively with serum Na and Ca and negatively with serum K, respectively. Hair HM analysis was used as a bio-indicator for monitoring body HM status from past environmental HM exposure in which CVDs risk factors were observed to correlate positively with higher hair concentrations of Zn, Fe, Mo, Pb, As, Ca and Na and negatively with lower hair concentrations of Cu, Mg, Mn and K in MI patients, respectively. Thus, higher hair concentrations of Zn and Pb indicate their higher environmental exposure and possible cause of higher CVDs risk factors in MI patients from Mandi-Gobindgarh.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aldosterone; C-Reactive Protein; Cardiovascular Diseases; China; Cholesterol, HDL; Electrolytes; Environmental Monitoring; Humans; Lead; Metals, Heavy; Myocardial Infarction; Risk Assessment; Risk Factors; Steel; Triglycerides

The association between urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative stress marker, and the incidence of cardiovascular disease (CVD) has not been confirmed because no previous studies evaluated 24-hour 8-OHdG excretion levels in the general population. We aimed to confirm the association between 24-hour urinary 8-OHdG levels and CVD risk among Japanese men and women.. A nested case-control study was performed based on a 24-hour urine collection in a community-based cohort study performed from 1996 to 2005. Seventy-six cases (55 men and 21 women) who experienced their first CVD incidence during the follow-up period (median: 5.9 years) were recruited. The controls were frequency-matched 1:2, with each case for sex, age, area of residence, and baseline year. The 8-OHdG level was measured by enzyme-linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression models adjusted for body mass index, ethanol intake, smoking status, and estimated glomerular filtration rate.. The geometric mean and geometric standard deviation (SD) of 8-OHdG levels (nmol/day) for cases and controls were 35.5 (1.55) and 35.5 (1.54) for men and 32.1 (1.35) and 25.0 (1.39) for women, respectively. The multivariable OR (95% CI) of CVD incidence according to the 1-SD increment of the log-transformed 8-OHdG level was 2.08 (0.99-4.37) for women. The multivariable ORs (95% CIs) for the 1st (lowest) and 4th versus 2nd quartile according to 8-OHdG for men were 3.29 (1.02-10.61) and 2.77 (0.96-7.96), respectively.. A high 8-OHdG level tended to be associated with CVD incidence among women.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Body Mass Index; Cardiovascular Diseases; Case-Control Studies; Ethanol; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Incidence; Japan; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Oxidative Stress; Regression Analysis; Risk

8-Oxo-2'-deoxyguanosine (8-oxo-2'-dG) is a biomarker of oxidative DNA damage that is associated with cardiovascular disease and premature mortality in the general population. Although oxidative stress has a proven role in cardiovascular complications in diabetes mellitus, evidence for a relationship between plasma 8-oxo-2'-dG and major cardiovascular outcomes in diabetes mellitus is weak.. A case-cohort study was performed in 3766 participants with prevalent diabetes mellitus in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) trial (ClinicalTrials.gov number NCT00145925). The hazard ratios for mortality and major acute cardiovascular events were derived using Cox regression models. During a median of 5 years of follow-up, 695 (18.4%) participants in this enriched cohort died (including 354 deaths from cardiovascular disease). Individuals with higher levels of 8-oxo-2'-dG were more likely to die. After adjusting for cardiovascular disease risk factors, the hazard ratio for a 1-SD increase in plasma 8-oxo-2'-dG was 1.10 (95% confidence interval, 1.01-1.20;. In adults with type 2 diabetes mellitus, increased levels of 8-oxo-2'-dG are independently associated with all-cause mortality and cardiovascular mortality in adults with longstanding type 2 diabetes mellitus who participated in the ADVANCE trial, consistent with the role of oxidative damage in the development and progression of cardiovascular decompensation in diabetes mellitus.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00145925.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; Cardiovascular Diseases; Cause of Death; Deoxyguanosine; Diabetes Mellitus, Type 2; DNA Damage; Female; Humans; Male; Middle Aged; Oxidative Stress; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors; Up-Regulation

Topics: 8-Hydroxy-2'-Deoxyguanosine; Angiotensins; Animals; Arginine; Cardiovascular Diseases; Deoxyguanosine; Disease Models, Animal; Humans; Hypertension; Hypoxia; Kidney; Male; Mice; Mice, Inbred C57BL; Norepinephrine; Oxidative Stress; Sympathectomy; Sympathetic Nervous System

The objectives of this prospective study were: 1) to determine the prevalence and determinants of obstructive sleep apnoea (OSA) in patients with newly diagnosed idiopathic pulmonary fibrosis (IPF); 2) to determine whether OSA was associated with cardiovascular disease (CVD) as well as increased oxidative stress and levels of IPF biomarkers in the blood.A group of 45 patients with newly diagnosed IPF attended polysomnography. The prevalence of CVD and the severity of coronary artery calcification were investigated by high-resolution computed tomography. The levels of 8-hydroxydeoxyguanosine (8-OH-DG) and various IPF biomarkers in the blood were compared between patients with no or mild OSA (apnoea-hypopnoea index (AHI) <15 events·h

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Biomarkers; Calcinosis; Cardiovascular Diseases; Comorbidity; Coronary Vessels; Deoxyguanosine; Female; France; Humans; Idiopathic Pulmonary Fibrosis; Male; Middle Aged; Oxidative Stress; Polysomnography; Prevalence; Prospective Studies; Risk; Sleep Apnea, Obstructive; Tomography, X-Ray Computed

Coronary artery bypass grafting (CABG), one of the most common cardiac surgical procedures, is characterized by a burst of oxidative stress. 8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), produced following DNA repairing, is used as an indicator of oxidative DNA damage in humans. The effect of CABG on oxidative-induced DNA damage, evaluated through the measurement of urinary 8-oxodG by a developed and validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in 52 coronary artery disease (CAD) patients, was assessed before (T0), five days (T1), and six months (T2) after CABG procedure. These results were compared with those obtained in 40 subjects with cardiovascular risk factors and without overt cardiovascular disease (CTR). Baseline (T0) 8-oxodG was higher in CAD than in CTR (

Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Cardiovascular Diseases; Deoxyguanosine; DNA Damage; Free Radicals; Humans; Male; Middle Aged; Risk Factors

The association between early exposure to ambient air pollution and adverse pregnancy outcomes in China is unclear. This study will assess the risk of early-life exposure to air pollutants in Beijing and explore the viability of 8-hydroxydeoxyguanosine (8-OHdG) as a biological indicator to assess oxidative stress induced by early-life exposure to air pollution.. Here. This research protocol has already been approved by the Medical Ethics Committee of Beijing Obstetrics and Gynecology Hospital. Written informed consent will be obtained from all study participants prior to enrolment. The results will be published in peer-reviewed journals or disseminated through conference presentations.. This study has been registered in WHO International Clinical Trial Register-Chinese Clinical Trial Registry under registrationnumber ChiCTR-ROC-16010181 (http :// www.chictr.org.cn / showproj.aspx ?proj=17328).

Topics: 8-Hydroxy-2'-Deoxyguanosine; Air Pollutants; Air Pollution; Beijing; Cardiovascular Diseases; Deoxyguanosine; Environmental Monitoring; Female; Humans; Infant; Infant, Newborn; Maternal Exposure; Particulate Matter; Pregnancy; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Proportional Hazards Models; Prospective Studies; Research Design; Respiratory Tract Diseases

Considerable evidence suggests that periodic limb movements during sleep (PLMS) are associated with cardiovascular risk and poor stroke outcome. However, the pathogenesis for this association in stroke patients remains largely unknown.. This cross-sectional study enrolled 112 consecutive patients who were admitted to rehabilitation ward due to ischemic stroke. Polysomnography and laboratory tests for oxidative stress and inflammatory biomarkers including C-reactive protein, interleukin 6, total antioxidant capacity (TAC), and urinary 8-hydroxy-2-deoxyguanosine were conducted.. Patients were stratified into three categories according to their PLMS index. Patients in the PLMS index ≥15 group were significantly older (P = 0.011), presented a significantly higher National Institute of Health Stroke Scale at stroke onset (P = 0.032), and lower Barthel index (P = 0.035) than patients in the PLMS index <5 group. The level of TAC differed significantly (P = 0.018) among the three groups. Multivariate linear regression analyses show that the PLMS index was negatively and independently correlated with TAC (P = 0.024) in women. Besides, multivariate logistic regression analyses also reveal that patients with a PLMS index ≥15 compared with the referent PLMS index <5 had a 7.58-fold increased relative hazard for stroke recurrence (odds ratio 7.58, [1.31-43.88], P = 0.024).. This study suggests that PLMS was independently associated with decreased antioxidant capacity in women with ischemic stroke.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Deoxyguanosine; Female; Humans; Interleukin-6; Middle Aged; Nocturnal Myoclonus Syndrome; Oxidative Stress; Risk Factors; Stroke

Amounts of DNA damage and homocysteine (Hcy) in heart patients blood may have strong function in the causation of cardiovascular disease (CVD). The main objective of this work was to know experimentally the role of total oxidants (produced by Reactive Oxygen species (ROS), clinical biochemical indices, their oxidized products and total antioxidant status (TAS) among such patients to find the association of homocysteine, total oxidation status (TOS) and oxidative DNA damage with other clinical parameters in sixty positive CVD patients compared with those of 60 normal subjects. As compared to healthy individuals, CVD patients had significantly higher concentrations of homocysteine (p<0.0001), total oxidants stress (TOS) (p<0.0001), serum total lipids (p<0.04), malondialdehyde (MDA) (p<0.001), high density lipoprotein-cholesterol (HDL-C) (p<0.0001), and low density lipoprotein cholesterol (LDL-C) (p<0.01), than those of healthy individuals. Plasma Hcy content, TOS and amount of DNA were positively and significantly associated with cholesterol, triglycerides, systolic blood pressure, urea, and albumin (p values<0.01). TOS, Hcy and oxidative DNA damage were negatively correlated with HDL-c, TAS and proteins. It is suggested that these parameters have pivotal role in diagnostic process of determining severity in CAD patients. Oxidized products of macromolecules in blood of CVD patients impart major functions in causing CVD disease.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Deoxyguanosine; DNA Damage; Female; Homocysteine; Humans; Lipids; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Thiobarbituric Acid Reactive Substances; Up-Regulation

Oxidative and nitrosative stress has suggested to be involved in the pathophysiology of cardiovascular diseases, but has unclear relationship with the risk for incident stroke.. In this nested case-control study, cases consisted of 131 participants who were free of stroke at screening and experienced incident stroke during the follow-up period. Controls were 1:1 frequency-matched for age and sex. Baseline levels of urinary creatinine-indexed biomarkers were measured using liquid chromatography-tandem mass spectrometry, including 8-iso-prostaglandin F₂α (8-iso-PGF₂α), 4-hydroxynonenal conjugate with mercapturic acid, 8-hydroxydeoxyguanosine and 8-nitroguanine.. The levels of urinary 8-iso-PGF₂α in stroke cases were higher than in controls [median (interquartile range), 1.13 (2.23-4.36) μg/g creatinine versus 0.71 (1.34-3.02) μg/g creatinine, p=0.004]. After adjusting cardiovascular risk factors, the association remained that higher level of urinary 8-iso-PGF₂α entailed the greater risk for incident stroke [per 1 standard deviation increase in log-transformed value, adjusted odds ratio, 1.40; 95% confidence interval (CI), 1.06-1.85; p=0.005] with a significant increasing trend across its quartiles (p for trend=0.016). After adding urinary 8-iso-PGF₂α, the prediction model not only improved discrimination between participants with or without incident stroke (integrated discrimination improvement, 0.025; 95% CI, 0.006-0.045; p=0.005), but enhanced stroke risk stratification (net reclassification improvement, 19.8%; 95% CI, 4.6-35.1%; p=0.011). In contrast, the relationships were non-significant among the other three biomarkers.. Our findings demonstrated that urinary 8-iso-PGF₂α could be an independent biomarker of oxidative stress for prediction of the risk for incident stroke.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Aldehydes; Biomarkers; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Case-Control Studies; Chromatography; Creatinine; Deoxyguanosine; Dinoprost; Female; Guanine; Humans; Male; Middle Aged; Oxidative Stress; Predictive Value of Tests; Prospective Studies; Risk Factors; Stroke; Tandem Mass Spectrometry

The urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG) reflect the oxidation status of hypertensive subjects and it can be used for monitoring oxidative stress changes. However, the influence of cardiovascular risk factors and inflammation on the urinary levels of this marker in hypertension (HT) has never evaluated. The purpose of this study was to analyze the impact of cardiovascular risk factors, and established inflammatory markers on 8-OHdG in essential HT.. We studied 149 asymptomatic hypertensive patients (61 ± 14 years). A routine physical examination, laboratory analyses, and echo-Doppler study were performed. Urinary 8-OHdG and plasma tumor necrosis factor-α (TNF-α), soluble TNF receptor 1 (sTNF-R1), soluble TNF receptor 2 (sTNF-R2), and interleukin-6 (IL-6) were determined.. 8-OHdG/creatinine levels were higher in hypertrophic patients (P = 0.022) and correlated with left ventricular mass index (P < 0.01). When 8-OHdG/creatinine was compared according to obesity and diabetes in our hypertensive subjects, no significant differences were found. 8-OHdG/creatinine was increased in hypertensive smokers (P = 0.032) and women (P = 0.006). Furthermore, 8-OHdG/creatinine correlated with TNF-α, sTNF-R1, sTNF-R2 (P < 0.0001), and with IL-6 (P < 0.05). A multivariate linear regression analysis showed that gender, smoking, and TNF-α were independent factors of 8-OHdG/creatinine.. Urinary 8-OHdG was increased in hypertensive patients with hypertrophy even under medical treatment. The presence of other cardiovascular risk factors on top of HT do not alter the concentrations of this oxidative stress marker, only smoking increasing its levels. TNF-α is an independent factor of 8-OHdG. These data suggest that this urinary marker gives specific additional information, further than blood pressure control alone, when evaluating hypertensive patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Biomarkers; Blood Pressure; Cardiovascular Diseases; Deoxyguanosine; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Inflammation; Interleukin-6; Male; Middle Aged; Obesity; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Risk Factors; Tumor Necrosis Factor-alpha

The aim of the current study was to examine the relationship between clinical markers of inflammation and 8-oxo-7,8-dihydro-2'deoxyguanosine (8-oxodG), an oxidative stress marker, in middle-aged women drawn from the HANDLS study, a longitudinal epidemiological study.. We examined commonly assayed markers of inflammation, the DNA base adduct 8-oxodG, a marker of oxidative stress, and cardiovascular risk factors in a cohort of women matched on age and race in 3 groups (n=39 per group) who had low (<3 mg/L) high-sensitivity C-reactive protein (hsCRP), mid (>3-20 mg/L), and high (>20 mg/L) hsCRP. We found a significant relationship between hsCRP level and the oxidative stress marker, 8-oxodG. 8-oxodG was positively correlated with systolic blood pressure, pulse pressure, and interleukin-23. hsCRP was associated with obesity variables, high-density lipoprotein, serum insulin levels, interleukin-12p70 and intracellular adhesion molecule-1. Incubation of primary human endothelial cells with hsCRP generated reactive oxygen species in vitro. Furthermore, hsCRP specifically induced DNA base lesions, but not other forms of DNA damage, including single and double strand breaks.. These data suggest that in women 8-oxodG is associated with hsCRP and is independently related to select cardiovascular risk factors. Our data in women suggest that hsCRP may contribute to cardiovascular disease by increasing oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Baltimore; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Cells, Cultured; Deoxyguanosine; DNA Damage; Female; Human Umbilical Vein Endothelial Cells; Humans; Inflammation Mediators; Logistic Models; Longitudinal Studies; Middle Aged; Odds Ratio; Oxidative Stress; Reactive Oxygen Species; Risk Assessment; Risk Factors; Sex Factors

Increased vascular calcification and oxidative stress are considered as extra renal risk factors at the pathogenesis cardiovascular events in chronic kidney disease (CKD). We investigated matrix Gla protein (MGP) (T-138C, Glu60X, Thr83Ala) and Klotho (Cys370Ser) gene polymorphisms, serum MGP levels, and oxidative stress status of 84 CKD patients and 37 healthy controls. The MGP gene Glu60X and Thr83Ala polymorphisms were significantly associated with CKD. The correlation between T-138C genotype of MGP gene, Cys370Ser genotype of Klotho gene, and CKD was not significant (p > 0.05). At the haplotype analysis, the combination of the X allele of Glu60X and the Thr allele of Thr83Ala showed a significantly increased risk of CKD (p < 0.05). X allele, Thr allele, and C allele of T-138C were associated with diabetes mellitus and CKD phenotypes occurring concurrently (p < 0.01). Serum zinc levels were significantly low in end-stage renal disease (ESRD) patients (p = 0.0001). The total comet score frequency of ESRD patients was higher than that of control group (p < 0.05). The urinary 8-hydroxy-2'-deoxyguanosine levels were significantly high in CKD patients (p < 0.05). According to this study, analyzing the distribution of MGP gene and oxidative stress status would be very informative in order to detect their role at CKD.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aged, 80 and over; Calcium-Binding Proteins; Cardiovascular Diseases; Case-Control Studies; Cohort Studies; Deoxyguanosine; Extracellular Matrix Proteins; Female; Genotype; Glucuronidase; Humans; Kidney Failure, Chronic; Klotho Proteins; Male; Matrix Gla Protein; Middle Aged; Oxidative Stress; Polymerase Chain Reaction; Polymorphism, Genetic; Prognosis; Reference Values; Renal Dialysis; Renal Insufficiency, Chronic; Severity of Illness Index; Statistics, Nonparametric; Young Adult

The objective of the study was to evaluate oxidative stress (OS) status in subjects with different cardiovascular risk factors. With this in mind, we have studied three models of high cardiovascular risk: hypertension (HT) with and without metabolic syndrome, familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH) with and without insulin resistance. Oxidative stress markers (oxidized/reduced glutathione ratio, 8-oxo-deoxyguanosine and malondialdehide) together with the activity of antioxidant enzyme triad (superoxide dismutase, catalase, glutathione peroxidase) and activation of both pro-oxidant enzyme (NAPDH oxidase components) and AGTR1 genes, as well as antioxidant enzyme genes (CuZn-SOD, CAT, GPX1, GSR, GSS and TXN) were measured in mononuclear cells of controls (n = 20) and patients (n = 90) by assessing mRNA levels. Activity of some of these antioxidant enzymes was also tested. An increase in OS and pro-oxidant gene mRNA values was observed in patients compared to controls. The hypertensive group showed not only the highest OS values, but also the highest pro-oxidant activation compared to those observed in the other groups. In addition, in HT a significantly reduced antioxidant activity and mRNA induction of antioxidant genes were found when compared to controls and the other groups. In FH and FCH, the activation of pro-oxidant enzymes was also higher and antioxidant ones lower than in the control group, although it did not reach the values obtained in hypertensives. The thioredoxin system was more activated in patients as compared to controls, and the highest levels were in hypertensives. The increased oxidative status in the presence of cardiovascular risk factors is a consequence of both the activation of pro-oxidant mechanisms and the reduction of the antioxidant ones. The altered response of the main cytoplasmic antioxidant systems largely contributes to OS despite the apparent attempt of the thioredoxin system to control it.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Cardiovascular Diseases; Catalase; Deoxyguanosine; Female; Gene Expression Profiling; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Glutathione Synthase; Humans; Hyperlipidemia, Familial Combined; Hyperlipoproteinemia Type II; Hypertension; Male; Malondialdehyde; Middle Aged; NADPH Oxidases; Oxidative Stress; Phosphoproteins; Risk Factors; Superoxide Dismutase

It is known that vitamin E and some carotenoids have antioxidant activities that alleviate endothelial dysfunction and play a protective role against cardiovascular disease. The current study was designed to examine the hypothesis that astaxanthin, a red pigment carotenoid found in salmonid and crustacean aquaculture, protects stroke-prone spontaneously hypertensive rats (SHRSP) from vascular oxidative damage, hypertension, and cerebral thrombosis. Male 6-week-old SHRSP were classified into 4 groups: a control group, 2 astaxanthin groups, and a vitamin E group. The treated animals were given either astaxanthin or vitamin E for 3 weeks. Body weights in each group were not significantly different from control group during the treatment period, but the usual increase in systolic blood pressure in SHRSP observed with age was significantly suppressed by treatment. Thrombogenesis, assessed using a helium-neon (He-Ne) laser technique in pial blood vessels, together with antioxidant activity, assessed by measuring urinary 8-OHdG levels, were significantly moderated. Urinary nitric oxide (NO) metabolites were increased after treatment. These results supported our hypothesis and strongly suggested that the antithrombotic and antihypertensive effects of astaxanthin or vitamin E may be related to an increase in bioavailable NO, possibly mediated by decreased inactivation of NO by reactive oxygen species.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antihypertensive Agents; Antioxidants; Cardiovascular Diseases; Deoxyguanosine; Dose-Response Relationship, Drug; Fibrinolytic Agents; Hypertension; Intracranial Thrombosis; Male; Nitrates; Nitric Oxide; Nitrites; Oxidative Stress; Rats; Rats, Inbred SHR; Risk Factors; Specific Pathogen-Free Organisms; Stroke; Xanthophylls

Low vitamin B-6 status has been linked to an increased risk of cardiovascular diseases. The cardioprotective effects of vitamin B-6 independent of homocysteine suggest that additional mechanisms may be involved.. Our objective was to examine the cross-sectional association of vitamin B-6 status with markers of inflammation and oxidative stress.. We measured plasma pyridoxal-5'-phosphate (PLP), C-reactive protein (CRP), and an oxidative DNA damage marker, urinary 8-hydroxydeoxyguanosine (8-OHdG), in Puerto Rican adults who were living in Massachusetts (n = 1205, aged 45-75 y).. There was a strong dose-response relation of plasma PLP concentration with plasma CRP. Increasing quartiles of PLP were significantly associated with lower CRP concentrations (geometric means: 4.7, 3.6, 3.1, and 2.5 mg/L; P for trend < 0.0001) and with lower urinary 8-OHdG concentrations (geometric means: 124, 124, 117, and 108 ng/mg creatinine; P for trend: 0.025) after multivariate adjustment. These negative associations persisted after plasma homocysteine was controlled for. Plasma PLP concentrations were significantly correlated with plasma fasting glucose (r = -0.1, P = 0.0006), glycated hemoglobin (r = -0.08, P = 0.006), and homeostasis model assessment of beta cell function (r = 0.082, P = 0.005). Metabolic syndrome, obesity, and diabetes were also significantly associated with low plasma PLP concentrations (P = 0.011, 0.0007, and 0.004, respectively).. Low vitamin B-6 concentrations are associated with inflammation, higher oxidative stress, and metabolic conditions in older Puerto Rican adults. Our data suggest that vitamin B-6 may influence cardiovascular disease risk through mechanisms other than homocysteine and support the notion that nutritional status may influence the health disparities present in this population.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Boston; C-Reactive Protein; Cardiovascular Diseases; Cross-Sectional Studies; Deoxyguanosine; Female; Hispanic or Latino; Humans; Inflammation; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress; Pyridoxal Phosphate; Statistics, Nonparametric; Vitamin B 6

Although not all findings are consistent, growing evidence suggests that individuals high in dispositional hostility are at elevated risk for cardiovascular disease and all-cause mortality; however, the mechanisms of these associations remain unclear. One possibility is that hostility is associated with oxidative stress. Here, we explore relationships between hostility and a measure of systemic oxidative stress among a mid-life sample.. In a community sample of 223 adults aged 30 to 54 years (86% white, 50% female), oxidative stress was measured as the 24-hour urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG). An abbreviated Cook Medley Hostility Scale was used to measure dimensions of hostility.. Regression analyses controlling for demographic characteristics and cardiovascular risk factors showed a positive relationship of 8-OHdG with total hostility (beta = 0.003, p = .03) and hostile affect (beta = 0.018, p < .001).. These findings provide evidence that dispositional hostility, and in particular, hostile affect, covary positively with systemic oxidative stress, raising the possibility that oxidative stress contributes to the pathogenicity of hostile attributes.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Affect; Age Factors; Attitude; Biomarkers; Cardiovascular Diseases; Circadian Rhythm; Data Collection; Deoxyguanosine; DNA Damage; Epinephrine; Female; Hostility; Humans; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Personality; Personality Inventory; Risk Factors; Volunteers

There is now evidence that major depression and myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are accompanied by partially overlapping pathophysiological mechanisms, i.e. activation of various inflammatory and oxidative & nitrosative (IO&NS) pathways.. The aim of the present study was to examine the urinary excretion of 8-hydroxy-deoxyguanosine (8-OhdG), a marker of oxidative damage to DNA, in depression; ME/CFS; and depression and ME/CFS.. Toward this end, morning urine was sampled for the assays of 8-OHdG and creatinine, in 44 patients with ME/CFS; 25 with major depression; 23 with depression and ME/CFS; and 17 normal controls. Severity of fatigue and somatic symptoms was measured by means of the Fibromyalgia and CFS Rating (FF) scale.. We found that 49.0% of the variance in the urinary excretion of 8-OHdG was predicted by the regression on creatinine. Consequently, the urinary 8-OHdG excretion should be expressed as the residualized 8-OHdG values after partialling out the effects of creatinine and not by computing the 8-OHdG / creatinine ratio. We found that the residualized urinary excretion of 8-OHdG (adjusted for creatinine) was significantly higher in patients with depression and ME/CFS than in normal controls and all other patients. In the patient group, there were significant correlations between the urinary 8-OHdG and the total score on the FF scale and sadness and flu-like malaise.. The findings show increased oxidatively generated DNA damage in patients with major depression and ME/CFS and, therefore, further extent the role played by IO&NS pathways in the pathophysiology of both disorders. Since oxidatively damage to DNA is a risk factor for atherosclerosis and neurodegeneration, our results also explain previous findings on increased cardiovascular morbidity in depression and ME/CFS, and neurodegenerative processes in depression.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Cardiovascular Diseases; Creatinine; Depressive Disorder, Major; DNA Damage; Enzyme-Linked Immunosorbent Assay; Fatigue Syndrome, Chronic; Female; Guanine; Humans; Lipid Peroxidation; Male; Middle Aged; Morbidity; Oxidative Stress; Reactive Nitrogen Species; Reactive Oxygen Species; Risk Factors; Severity of Illness Index

Individuals with type 2 diabetes exhibit higher DNA damage and increased risk of cardiovascular disease (CVD). However, mechanisms underlying the association between DNA damage and development of type 2 diabetes and CVD are not understood. We sought to link peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PPARGC1A), a master transcriptional regulator of mitochondrial oxidative phosphorylation and cellular energy metabolism, with DNA damage, type 2 diabetes, and CVD.. We measured DNA damage as urinary 8-hydroxydeoxyguanosine (8-OHdG) concentration and examined the relationship between nine PPARGC1A genetic variants, DNA damage, type 2 diabetes, and self-reported CVD in 959 participants of the Boston Puerto Rican Health Study.. With respect to urinary 8-OHdG, PPARGC1A variants showed significant association, and PPARGC1A haplotypes exhibited significant association after correction for multiple testing. Two independent PPARGC1A variants associated significantly with type 2 diabetes (odds ratios [ORs] 1.35 and 2.46; P = 0.045 and <0.001). Carriers of minor alleles of two other PPARGC1A variants, both in strong linkage disequilibrium and associated with lower DNA damage, showed lower prevalence of CVD (ORs 0.53 and 0.65; P = 0.030 and 0.175). Moreover, we found that physical activity correlated negatively with DNA damage.. It is plausible that low physical activity combined with risk haplotyes contribute to the high prevalence of type 2 diabetes in this population. We propose that PPARGC1A influences development of type 2 diabetes and CVD via DNA damage. Increasing physical activity, which induces PPARGC1A expression, is a potential strategy to slow DNA damage, thereby decreasing the risk of CVD for individuals with type 2 diabetes.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Biomarkers; Boston; Cardiovascular Diseases; Deoxyguanosine; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Angiopathies; DNA Damage; Exons; Female; Gene Frequency; Genetic Variation; Heat-Shock Proteins; Humans; Introns; Male; Middle Aged; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Polymorphism, Single Nucleotide; Puerto Rico; Risk Factors; Transcription Factors

The age-related impairment of endothelium-dependent vasodilatation contributes to increased cardiovascular risk in the elderly. For primary and secondary prevention, aspirin can reduce the incidence of cardiovascular events in this patient population. The present work evaluated the effect of low-dose aspirin on age-related endothelial dysfunction in C57B/J6 aging mice and investigated its protective antioxidative effect. Age-related endothelial dysfunction was assessed by the response to acetylcholine of phenylephrine-induced precontracted aortic segments isolated from 12-, 36-, 60-, and 84-wk-old mice. The effect of low-dose aspirin was examined in mice presenting a decrease in endothelial-dependent relaxation (EDR). The effects of age and aspirin treatment on structural changes were determined in mouse aortic sections. The effect of aspirin on the oxidative stress markers malondialdehyde and 8-hydroxy-2'-deoxyguanosine (8-OhdG) was also quantified. Compared with that of 12-wk-old mice, the EDR was significantly reduced in 60- and 84-wk-old mice (P < 0.05); 68-wk-old mice treated with aspirin displayed a higher EDR compared with control mice of the same age (83.9 +/- 4 vs. 66.3 +/- 5%; P < 0.05). Aspirin treatment decreased 8-OHdG levels (P < 0.05), but no significant effect on intima/media thickness ratio was observed. The protective effect of aspirin was not observed when treatment was initiated in older mice (96 wk of age). It was found that low-dose aspirin is able to prevent age-related endothelial dysfunction in aging mice. However, the absence of this effect in the older age groups demonstrates that treatment should be initiated early on. The underlying mechanism may involve the protective effect of aspirin against oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acetylcholine; Age Factors; Aging; Animals; Antioxidants; Aorta; Aspirin; Cardiovascular Diseases; Deoxyguanosine; Dose-Response Relationship, Drug; Endothelium, Vascular; Male; Malondialdehyde; Mice; Mice, Inbred C57BL; Models, Animal; Oxidative Stress; Phenylephrine; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

Accumulation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) in DNA is associated with mutagenesis and cell death. Little attention has been given to the biological significance of 8-oxo-dG accumulation in cardiovascular tissues during the different stage of hypertension and its prevention. We thus investigated the levels and localization of both 8-oxo-dG accumulation and expression of MTH1, which hydrolyzes 8-oxo-dGTP to prevent its incorporation into DNA, in the thoracic aorta prepared from stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wister-Kyoto rats (WKY), aged 5-32 weeks. HPLC-MS/MS analysis revealed that the levels of nuclear 8-oxo-dG in the aorta increased significantly in SHRSP, but not WKY, with aging. Immunohistochemical study revealed that both TUNEL reactivity and 8-oxo-dG immunoreactivity were increased in smooth muscle cells (SMC) and endothelial cells (EC) of the aorta with aging, and they exhibited similar distributions in serial sections. The number of 8-oxo-dG and TUNEL positive cells in EC, but not in SMC, was significantly higher in SHRSP than WKY at 32 weeks of age. In contrast, the expression levels of Mth1mRNA and MTH1 protein in the aorta were similarly decreased both in SHRSP and WKY with aging. However, the number of MTH1 expressing EC was remarkably increased in the older SHRSP compared to the younger ones or age-matched WKY. Hypertension significantly increased not only 8-oxo-dG accumulation but also the expression of MTH1 in EC of the aorta during aging. While accumulation of 8-oxo-dG in SMC of the aorta was slightly increased, the expression of MTH1 protein in SMC was rather decreased by hypertension. We thus suggest that MTH1 may protect EC in the aorta from the oxidative damage increased by hypertension.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Apoptosis; Cardiovascular Diseases; Deoxyguanosine; Disease Models, Animal; DNA Repair; DNA Repair Enzymes; Hypertension; Immunohistochemistry; Male; Mutagenesis; Phosphoric Monoester Hydrolases; Rats; Rats, Inbred SHR; Rats, Inbred WKY

To clarify the mechanism of involvement of oxidative stress in hypertensives, we investigated the relationship between the marker of oxidative DNA damage, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and cardiovascular risk factors, such as hypertension and serum glycosylated hemoglobin (HbA1c), among Tanzanians aged 46-58 years who were not on antihypertensive medication.. Sixty subjects (males/females, 28/ 32) were selected randomly from the subjects who completed a 24h urine collection in our epidemiological study at Dar es Salaam, Tanzania in 1998. The subjects were divided into two groups, hypertensive subjects (systolic blood pressure (SBP) > or = 140 mmHg and/or diastolic blood pressure (DBP) > or =90 mmHg) and normotensive subjects (SBP < 140 mmHg and DBP < 90 mmHg) or hyperglycemic subjects (HbA1c > or = 6.0%) and normoglycemic subjects (HbA1c < 6.0%). Biological markers from urine and blood were analyzed centrally in the WHO Collaborating Center.. The mean levels of HbA1c and 8-OHdG were significantly higher in the hypertensive subjects than in the normotensive subjects (P < 0.05). Urinary 8-OHdG was significantly higher in hyperglycemic subjects than in normoglycemic subjects. HbA1c was positively correlated with the 24-h urinary 8-OHdG excretions (r= 0.698, P < 0.0001).. These findings suggest oxidative DNA damage is increased in hypertensive subjects, and there is a positive correlation between the level of blood glucose estimated as HbA1c and oxidative DNA damage. Hyperglycemia related to insulin resistance in hypertension in Tanzania is associated with increased urinary 8-OHdG.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Cardiovascular Diseases; Circadian Rhythm; Deoxyguanosine; DNA Damage; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypertension; Male; Middle Aged; Oxidative Stress; Risk Factors; Tanzania