Oxidant Stress and Aspirin-Insensitive Thromboxane Biosynthesis in Severe Unstable Angina

Cipollone, Francesco; Ciabattoni, Giovanni; Patrignani, Paola; Pasquale, Massimo; Gregorio, Domenico Di; Bucciarelli, Tonino; Davı̀, Giovanni; Cuccurullo, Franco; Patrono, Carlo

doi:10.1161/01.cir.102.9.1007

Cited by 204 publications

(121 citation statements)

References 38 publications

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“…Here we confirm the increase in F 2 -isoprostane excretion previously documented in hypercholesterolemia, 23,24 as well as in other conditions characterized by enhanced lipid peroxidation, such as type 2 diabetes, 20 unstable angina, 32 or heavy smoking. 21,22 Concomitant with the expected reductions in lipid levels, simvastatin reduced the elevated levels of 8-iso-PGF 2␣ by approximately one third, to levels found in healthy individuals, 20,21 mild smokers who were healthy, 22,25 or subjects with stable coronary artery disease.…”

Section: Discussionsupporting

confidence: 91%

Low-Density Lipoprotein Level Reduction by the 3-Hydroxy-3-Methylglutaryl Coenzyme-A Inhibitor Simvastatin Is Accompanied by a Related Reduction of F ₂ -Isoprostane Formation in Hypercholesterolemic Subjects

et al. 2002

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Background-Both statins and vitamin E, by reducing the rate of lipid peroxidation, may interfere with oxidative stress, but the impact of their combination is unknown. Methods and Results-We randomized 43 hypercholesterolemic patients (21 men, 22 women, age 63Ϯ11 years) to either simvastatin, to achieve Ͼ20% reduction of total cholesterol, or simvastatin plus 600 mg/d vitamin E for 2 months. Patients were then crossed over to the alternative treatment. Lipid parameters documented patients' compliance to simvastatin, whereas plasma levels of vitamin E documented compliance and absorption of vitamin E. We assessed urinary excretion of the isoprostane 8-iso-prostaglandin F 2␣ (8-iso-PGF 2␣ ) as an in vivo index of oxidative stress at baseline and after each month of therapy. 8-Iso-PGF 2␣ was significantly reduced by simvastatin, from 361Ϯ148 pg/mg creatinine (meanϮSD) at baseline to 239Ϯ124 pg/mg creatinine after 1 month.

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Section: Discussionsupporting

confidence: 91%

Low-Density Lipoprotein Level Reduction by the 3-Hydroxy-3-Methylglutaryl Coenzyme-A Inhibitor Simvastatin Is Accompanied by a Related Reduction of F ₂ -Isoprostane Formation in Hypercholesterolemic Subjects

et al. 2002

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“…On the other hand, it is also known that the plaque itself could release, once activated, biochemical substances such as, for instance, pro-oxidants, 26 -28 which, in turn, can stimulate the apoptotic process. 29 -31 The already accepted association between oxidative stress and ACS 32 together with the present finding that coincubation with Trolox markedly reduced the proapoptotic effect of serum would support this hypothesis.…”

Section: Original Findingssupporting

confidence: 64%

Serum From Patients With Acute Coronary Syndromes Displays a Proapoptotic Effect on Human Endothelial Cells

et al. 2003

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Background-Endothelial apoptosis of atherosclerotic lesions is a possible determinant for the stable-to-vulnerable plaque transition.Recent data support the notion that plaque activation may be a pan-coronary process, advocating the existence of circulating triggers. Methods and Results-Serum from 40 healthy subjects (group 1) and 73 patients with stable angina (nϭ32; group 2) or acute coronary syndromes (nϭ41; group 3) was incubated with human umbilical vein endothelial cells. The percentage of apoptosis by flow cytometry and Fas, Bax, and Bcl-2 protein expression by immunoblotting were evaluated at entry in patients and control subjects and repeated after 12 months in group 3. At baseline, apoptotic nuclei were higher in group 3 (14Ϯ6%) than in group 2 (3.3Ϯ1.8%) and group 1 (1.35Ϯ0.8%) (PϽ0.001). Fas and Bcl-2 were increased in group 3 with respect to groups 1 and 2 (PϽ0.01). Coincubation of group 3 serum with anti-tumor necrosis factor-␣ and anti-interleukin-6 monoclonal antibodies did not affect the human umbilical vein endothelial cell apoptotic process, whereas addition of Trolox decreased apoptosis to Ͻ50%. The percentage of apoptosis in group 3 significantly correlated to the numbers of coronary complex lesions at angiography (rϭ0.58, PϽ0.0005). In group 3, apoptosis and the Bax/Bcl-2 ratio decreased at 1 year (PϽ0.0001, PϽ0.05 respectively). Conclusions-Serum from patients with acute coronary syndromes displays a proapoptotic effect on human endothelial cells, supporting the theory of the existence of circulating triggers potentially able to activate atherosclerotic lesions.

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“…These findings suggested that there is a close relation between CAD and oxidative stress. In addition, the results are in agreement with previous studies (28,29) and demonstrate that coronary atherosclerosis may be associated with increased oxidative stress. The mechanisms responsible for the association between CAD and oxidative stress are unknown.…”

Section: Discussionsupporting

confidence: 92%

Increased Plasma Levels of Thioredoxin in Patients with Glucose Intolerance

et al. 2005

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Objective The aim of the present study was to determine the effects of glucose intolerance on oxidative stress in patients with coronary artery disease (CAD).Methods The patients were divided into 3 groups, diabetes mellitus (DM), IGT or normal glucose tolerance (NGT) according to the criteria of the American Diabetes Association.Patients The present study consisted of 178 consecutive patients who underwent diagnostic coronary arteriography and a 75-g glucose tolerance test.Results The level of plasma thioredoxin, a marker of oxidative stress was measured in every patient during the fasting state. The levels of plasma thioredoxin were significantly higher in the DM and IGT groups than the NGT group. Furthermore, we found that there was a positive association between thioredoxin levels and glycosylated hemoglobin ( =0.225, p=0.018). In multivariate logistic regression analysis, glucose intolerance (DM or IGT) was only independently associated with the high levels of thioredoxin. The levels of plasma thioredoxin were significantly higher in the CAD group compared to the non-CAD group. In multivariate logistic regression analysis, high levels of thioredoxin, male, age and hypertension were independently associated with the presence of CAD.Conclusion Glucose intolerance was associated with the high levels of thioredoxin. High levels of thioredoxin were related to the presence of CAD. The measurement of thioredoxin as the marker of oxidative stress may be useful for monitoring the development of the cardiovascular diseases.

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Oxidant Stress and Aspirin-Insensitive Thromboxane Biosynthesis in Severe Unstable Angina

Abstract: These findings establish a putative biochemical link between increased oxidant stress and aspirin-insensitive TX biosynthesis in patients with unstable angina and provide a rationale for dose-finding studies of antioxidants in this setting.

Cited by 204 publications

References 38 publications

Low-Density Lipoprotein Level Reduction by the 3-Hydroxy-3-Methylglutaryl Coenzyme-A Inhibitor Simvastatin Is Accompanied by a Related Reduction of F ₂ -Isoprostane Formation in Hypercholesterolemic Subjects

Low-Density Lipoprotein Level Reduction by the 3-Hydroxy-3-Methylglutaryl Coenzyme-A Inhibitor Simvastatin Is Accompanied by a Related Reduction of F ₂ -Isoprostane Formation in Hypercholesterolemic Subjects

Serum From Patients With Acute Coronary Syndromes Displays a Proapoptotic Effect on Human Endothelial Cells

Increased Plasma Levels of Thioredoxin in Patients with Glucose Intolerance

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Oxidant Stress and Aspirin-Insensitive Thromboxane Biosynthesis in Severe Unstable Angina

Abstract: These findings establish a putative biochemical link between increased oxidant stress and aspirin-insensitive TX biosynthesis in patients with unstable angina and provide a rationale for dose-finding studies of antioxidants in this setting.

Cited by 204 publications

References 38 publications

Low-Density Lipoprotein Level Reduction by the 3-Hydroxy-3-Methylglutaryl Coenzyme-A Inhibitor Simvastatin Is Accompanied by a Related Reduction of F 2 -Isoprostane Formation in Hypercholesterolemic Subjects

Low-Density Lipoprotein Level Reduction by the 3-Hydroxy-3-Methylglutaryl Coenzyme-A Inhibitor Simvastatin Is Accompanied by a Related Reduction of F 2 -Isoprostane Formation in Hypercholesterolemic Subjects

Serum From Patients With Acute Coronary Syndromes Displays a Proapoptotic Effect on Human Endothelial Cells

Increased Plasma Levels of Thioredoxin in Patients with Glucose Intolerance

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Low-Density Lipoprotein Level Reduction by the 3-Hydroxy-3-Methylglutaryl Coenzyme-A Inhibitor Simvastatin Is Accompanied by a Related Reduction of F ₂ -Isoprostane Formation in Hypercholesterolemic Subjects

Low-Density Lipoprotein Level Reduction by the 3-Hydroxy-3-Methylglutaryl Coenzyme-A Inhibitor Simvastatin Is Accompanied by a Related Reduction of F ₂ -Isoprostane Formation in Hypercholesterolemic Subjects