Oxidative-stress-mediated arterial dysfunction in patients with peripheral arterial disease

Loffredo, Lorenzo; Marcoccia, Antonella; Pignatelli, Pasquale; Andrea, Paola; Borgia, Maria Clotilde; Cangemi, Roberto; Chiarotti, Flavia

doi:10.1093/eurheartj/ehl533

Cited by 105 publications

(84 citation statements)

References 33 publications

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“…We also used an ELISA to assess 8‐oxo‐2′‐dG in plasma samples, as conventional chromatographic methods do not have the sensitivity to measure plasma levels. Although the circulating levels of 8‐oxo‐2′‐dG detailed in this study are similar to those reported in cross‐sectional studies using ELISA‐based assays in patients with diabetes mellitus25, 26, 27 and other settings,28, 29, 30, 31, 32 it is understood that ELISA overestimates 8‐oxo‐2′‐dG when compared with high‐sensitivity mass spectroscopy 33. This is partly because of the former method including DNA fragments containing 8‐oxo‐2′‐dG, in addition to free 8‐oxo‐2′‐dG, as well as the presence of interfering compounds in plasma.…”

Section: Discussionsupporting

confidence: 83%

Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial

Thomas

Woodward

et al. 2018

JAHA

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Background8‐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.Methods and ResultsA 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 (http://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; P=0.03). This was driven by an independent association between plasma 8‐oxo‐2′‐dG and cardiovascular death (hazard ratio, 1.23; 95% confidence interval, 1.10–1.37 [P<0.001]). By contrast, no association was seen between 8‐oxo‐2′‐dG and noncardiovascular disease death (of which cancer was the major single cause). 8‐Oxo‐2′‐dG was also not significantly associated with either nonfatal myocardial infarction or nonfatal stroke.ConclusionsIn 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.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00145925.

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Section: Discussionsupporting

confidence: 83%

Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial

Thomas

Woodward

et al. 2018

JAHA

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“…Recently, it was shown that endothelium-dependent vasodilation was impaired in subjects with elevated oxidative stress levels. 17,18) The present study demonstrated that the plasma 8-Iso-PG F2α levels were inversely correlated with plasma NO-metabolite concentration in the overall analysis of hypertensive and normotensive men. One hypothesis is that oxidative stress could be associated with endothelial dysfunction and reduced NO-production.…”

Section: Discussionmentioning

confidence: 49%

Oxidative Stress and Membrane Fluidity of Red Blood Cells in Hypertensive and Normotensive Men An Electron Spin Resonance Investigation

Tsuda

2010

Int. Heart J.

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SummaryRecent evidence indicates that oxidative stress might actively participate in the pathophysiology of hypertension, atherosclerosis, and other cardiovascular diseases. The purpose of the present study was to assess the possible link between oxidative stress and membrane fluidity in hypertensive and normotensive men. We measured the membrane fluidity (a reciprocal value of membrane microviscosity) of red blood cells (RBCs) in hypertensive and normotensive men using an electron spin resonance (ESR) and spin-labeling method. Membrane fluidity of RBCs was decreased in hypertensive men compared with normotensive men. The levels of plasma 8-Iso-prostaglandin F2α (8-Iso-PG F2α : an index of oxidative stress) were significantly higher in hypertensive men than in normotensive men. In contrast, plasma nitric oxide (NO)-metabolite levels were significantly lower in hypertensive men than in normotensive men. In the overall analysis of hypertensive and normotensive men, plasma 8-Iso-PG F2α levels were inversely correlated with plasma NO-metabolites. Furthermore, the reduced membrane fluidity of RBCs was associated with increased plasma 8-Iso-PG F2α and decreased plasma NO-metabolite levels. In a multivariate regression analysis, plasma 8-Iso-PG F2α was found to be an independent determinant of membrane fluidity of RBCs participate in the pathophysiology of hypertension and atherosclerosis, and might be associated with increased risk of cardiovascular diseases, vascular dysfunction, and the metabolic syndrome.1-3) Recent studies have shown that plasma 8-Iso-prostaglandin F2α (8-Iso-PG F2α ) may be a reliable index of oxidative stress in humans. [4][5][6][7] It was demonstrated that the plasma concentration of 8-Iso-PG F2α was significantly increased in subjects with essential hypertension compared with normotensive subjects. 4,5) It has also been shown that plasma 8-Iso-PG F2α levels were elevated in patients with coronary artery disease, particularly in those with hypertension. 6,7) However, cellular mechanisms of oxidative stress in the pathophysiology of hypertension are not fully understood.Abnormalities in the physical properties of the cell membranes may underlie the defects that are strongly linked to hypertension, stroke, and other cardiovascular disease conditions. 8,9) An electron spin resonance (ESR) and spinlabeling method has been developed to evaluate the membrane fluidity (a reciprocal value of membrane microviscosity) and the perturbations of membrane function by external agents. 8,9) Using the ESR method, we have been performing a series of experiments regarding the membrane fluidity in subjects with essential hypertension. [9][10][11][12][13] The results suggest that the membrane fluidity of red blood cells (RBCs) was significantly lower in hypertensive subjects than in normotensive subjects, indicating that the cell membranes were stiffer and less fluid in essential hypertension. [9][10][11][12][13] Because the deformability of RBCs may be highly dependent on the membrane fluidity, 8) the reduction in...

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“…This in turn led to monocyte infiltration and a vicious cycle of increasing oxidant stress. Peripheral artery disease, like coronary artery disease, is also associated with evidence of oxidative stress and treatment with an antioxidant improved arterial flow parameters [84].…”

Section: Nox Enzymes and Atherosclerosismentioning

confidence: 99%

Nox enzymes, ROS, and chronic disease: An example of antagonistic pleiotropy

Lambeth¹

2007

Free Radical Biology and Medicine

590

454

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Oxidative-stress-mediated arterial dysfunction in patients with peripheral arterial disease

Abstract: This study shows that in PAD patients, oxidative stress is implicated in determining reduced FMD.

Cited by 105 publications

References 33 publications

Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial

Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial

Oxidative Stress and Membrane Fluidity of Red Blood Cells in Hypertensive and Normotensive Men An Electron Spin Resonance Investigation

Nox enzymes, ROS, and chronic disease: An example of antagonistic pleiotropy

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