dinoprost and Coronary-Artery-Disease

The widespread detection of elevated oxidative stress levels in many medical conditions has led to numerous efforts to design interventions to reduce its effects. Efforts have been wide-ranging, from dietary changes to administration of antioxidants, supplements, e.g., omega-3-fatty acids, and many medications. However, there is still no systemic assessment of the efficacy of treatments for oxidative stress reduction across a variety of medical conditions. The goal of this meta-analysis is, by combining multiple studies, to quantitate the change in the levels of the popular oxidative stress biomarker 8-iso-prostaglandin F

Topics: Antioxidants; Biomarkers; Coronary Artery Disease; Dietary Supplements; Dinoprost; Genetics, Population; Humans; Lipid Peroxidation; Oxidation-Reduction; Oxidative Stress

The lungs participate in the modulation of the circulating inflammatory factors induced by coronary artery bypass grafting. We investigated whether aprotinin-which has been suggested to interact with inflammation-influences lung passage of key inflammatory factors after coronary artery bypass grafting.. A total of 40 patients undergoing coronary artery bypass grafting were randomized into four groups according to aprotinin dose: (1) high dose, (2) early low dose, (3) late low dose, and (4) without aprotinin. Pulmonary artery and radial artery blood samples were collected for the evaluation of calculated lung passage (pulmonary artery/radial artery) of the pro-inflammatory factors interleukin 6 and interleukin 8, 8-isoprostane, myeloperoxidase and the anti-inflammatory interleukin 10 immediately after induction of anesthesia (T1), 1 min after releasing aortic cross clamp (T2), 15 min after releasing aortic cross clamp (T3), 1 h after releasing aortic cross clamp (T4), and 20 h after releasing aortic cross clamp (T5).. Pulmonary artery/radial artery 8-isoprostane increased in patients with high aprotinin dose as compared with lower doses (1.1 range 0.97 vs 0.9 range 1.39, p = 0.001). The main effect comparing high aprotinin dose with lower doses was significant (F(1, 38) = 7.338, p = 0.01, partial eta squared = 0.16) further supporting difference in the effectiveness of high aprotinin dose for pulmonary artery/radial artery 8-isoprostane.. According to the pulmonary artery/radial artery equation, the impact of aprotinin on 8-isoprostane after coronary artery bypass grafting is dose dependent. Aprotinin may aid the lung passage of circulating factors toward a beneficial anti-inflammatory milieu.

Topics: Aprotinin; Coronary Artery Bypass; Coronary Artery Disease; Dinoprost; Dose-Response Relationship, Drug; Hemostatics; Humans; Interleukins; Pulmonary Artery; Radial Artery

In coronary artery disease patients, enhanced external counterpulsation (EECP) improves peripheral arterial function and nitric oxide (NO) bioavailability, which have been implicated in the pathogenesis of abnormal glucose tolerance (AGT). We sought to evaluate the effects of EECP on outcomes of arterial function, glucose tolerance, and skeletal muscle morphology in subjects with AGT.. 18 subjects with AGT were randomly (2:1 ratio) assigned to receive either 7 wk (35 1-h sessions) of EECP (n = 12) or 7 wk of standard care (control; n = 6). Peripheral vascular function, biochemical assays, glucose tolerance, and skeletal muscle morphology were evaluated before and after EECP or control. EECP increased normalized brachial artery (27%) and popliteal artery (52%) flow-mediated dilation. Plasma nitrite/nitrate (NOx) increased (30%) and 8-isoprostane-PGF-F(2α), a marker of lipid peroxidation in the plasma, decreased (-23%). Fasting plasma glucose declined (-16.9 ± 5.4 mg/dl), and the homeostasis model assessment of insulin resistance (HOMA-IR) decreased (31%) following EECP. Plasma glucose 120 min after initiation of oral glucose tolerance testing decreased (-28.3 ± 7.3 mg/dl), and the whole body composite insulin sensitivity index (C-ISI) increased (21%). VEGF concentrations increased (75%), and vastus lateralis skeletal muscle biopsies demonstrated improvements in capillary density following EECP. No change was observed in cellular signaling pathways, but there was a significant increase GLUT-4 protein expression (47%) following EECP.. Our findings provide novel evidence that EECP has a beneficial effect on peripheral arterial function and glucose tolerance in subjects with AGT.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Blood Pressure; Brachial Artery; Capillaries; Coronary Artery Disease; Counterpulsation; Dinoprost; Glucose; Glucose Intolerance; Glucose Tolerance Test; Glucose Transporter Type 4; Glycemic Index; Humans; Insulin; Middle Aged; Muscle, Skeletal; Neovascularization, Pathologic; Nitric Oxide; Oxidation-Reduction; Phosphorylation; Popliteal Artery; Regional Blood Flow; Signal Transduction; Vascular Endothelial Growth Factor A; Vasodilation

The goal of this study was to investigate whether omega-3 polyunsaturated fatty acids (n-3 PUFA) are able to alter plasma fibrin clot properties and reduce thrombin formation in stable coronary artery disease patients undergoing percutaneous coronary intervention (PCI).. In an investigator-initiated, prospective, double-blind, placebo-controlled, randomized study, patients undergoing PCI who received standard pharmacotherapy were assigned to the treatment with 1 g/day n-3 PUFA (n = 30) or placebo (n = 24) for 1 month. Plasma fibrin clot permeability (K(s)); lysis time (t(50%)); prothrombin fragment 1.2; and peak thrombin generation from automated thrombogram, 8-isoprostaglandin F(2α) (8-iso-PGF(2α), an oxidative stress marker), and C-reactive protein were determined at baseline, 3 to 5 days after randomization, and 30 days after randomization. At baseline, both treatment groups did not differ significantly. A 1-month treatment with n-3 PUFA compared with placebo was associated with 15.3% higher K(s), indicating larger pores in the fibrin network (P = 0.0005); 14.3% shorter t(50%), indicating increased susceptibility to fibrinolysis (P<0.0001); 33.8% lower prothrombin fragment 1.2 (P = 0.0013); 13.4% lower peak thrombin generation (P = 0.04); and 13.1% lower 8-iso-PGF(2α) (P = 0.009). Treatment with n-3 PUFA had no effect on fibrinogen and C-reactive protein. After 1 month of treatment, fibrinogen (r = -0.53, P<0.0001), treatment assignment (r = 0.29, P = 0.006) and 8-iso-PGF(2α) (r = -0.27, P = 0.015) were independently associated with clot permeability (P<0.0001, R(2) = 0.66).. Adding n-3 PUFA to standard therapy in stable patients undergoing PCI significantly decreases thrombin formation and oxidative stress and favorably alters fibrin clot properties. These findings indicate novel antithrombotic effects induced by n-3 PUFA in humans.

Topics: Aged; Analysis of Variance; Angioplasty, Balloon, Coronary; Aspirin; Biomarkers; Blood Coagulation; C-Reactive Protein; Chi-Square Distribution; Clopidogrel; Coronary Artery Disease; Dinoprost; Double-Blind Method; Down-Regulation; Drug Therapy, Combination; Fatty Acids, Omega-3; Female; Fibrin; Humans; Linear Models; Male; Middle Aged; Oxidative Stress; Peptide Fragments; Platelet Aggregation; Platelet Aggregation Inhibitors; Poland; Prospective Studies; Prothrombin; Thrombin; Thrombosis; Ticlopidine; Time Factors; Treatment Outcome

Oxidative stress may promote chronic inflammation and contribute to accelerated atherogenesis in patients with coronary artery disease (CAD). Sulodexide, a glycosaminoglycan consisting primarily of heparin, has been shown to affect oxidative stress in experimental settings. The purpose of this pilot study was to determine the effect of sulodexide administration on oxidative stress, inflammation and plasma lipids in patients with proven stable CAD.. Fifty-six optimally treated male CAD patients (pts), mean age 57+/-6 yrs, were randomized to either 8 weeks of sulodexide treatment (SUL, n=28), or to a control group (n=28). At baseline and at the end of the study, all pts underwent full clinical and standard laboratory plasma level assessment of lipids, markers of inflammation, and 8-isoprostane, as a sensitive index of oxidative stress.. At entry the 2 groups did not differ significantly in terms of age, coronary risk factors, clinical status and concomitant medication. SUL treatment appeared to be safe and caused a significant decrease in the level of plasma 8-isoprostane (77.4 vs 44.5 pg/ml, p<0.0001) compared with controls (75.7 vs 68.3 pg/ml, p=NS). In contrast, neither LDL cholesterol (2.71 vs 2.72 mmol/l) and triglycerides (1.38 vs 1.43 mmol/l), nor markers of inflammation - fibrinogen (3.7 vs 3.6 g/l), C-reactive protein (0.14 vs 0.13 mg/l), leukocyte count (6.33 vs 6.32x10(9)/l) - were affected by SUL treatment.. Sulodexide administration resulted in significant reduction in oxidative stress in stable CAD patients, and neither the changes in cholesterol metabolism nor in systemic inflammation underlay this effect.

Topics: Antioxidants; Biomarkers; C-Reactive Protein; Coronary Artery Disease; Dinoprost; Fibrinogen; Glycosaminoglycans; Humans; Inflammation; Leukocyte Count; Lipids; Male; Middle Aged; Oxidative Stress; Pilot Projects

1. Previous clinical studies with prostaglandin I(2) (PGI(2)) analogue beraprost sodium suggested the potential effects on protection of cardiovascular events in patients with peripheral artery disease. Although the mechanism is not well known, experimental studies have shown protective effects of endothelial cells. This study was designed to examine the effects of beraprost sodium on vascular endothelial function in the forearm of patients with coronary artery disease. 2. Beraprost sodium (120 microg/day) was orally administered to 14 coronary artery disease patients for 4 weeks and then stopped for 4 weeks. Eleven control patients did not receive beraprost sodium treatment. Reactive hyperemia was induced in the forearm, endothelium-dependent vasodilatation was assessed by plethysmography, and urinary 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) was measured at baseline, 4 weeks and 8 weeks. 3. Both groups had similar reactive hyperemic responses at baseline. In the control group, reactive hyperemic response and urinary 8-iso-PGF(2alpha) remained unchanged for 8 weeks. In the beraprost group, maximum forearm blood flow increased significantly (P = 0.01) after 4 weeks of treatment and returned to baseline at 8 weeks. Duration of hyperemia increased significantly (P = 0.003) after 4 weeks, and remained greater than baseline at 8 weeks (P = 0.02). Urinary 8-iso-PGF(2alpha) decreased significantly (P = 0.03) after 4 weeks, and tended to be lower at 8 weeks (P = 0.07). Changes in reactive hyperemia correlated weakly but significantly with changes in 8-iso-PGF(2alpha) (P < 0.001). 4. Beraprost sodium decreased oxidative stress and improved forearm endothelium-dependent vasodilatation in coronary artery disease patients. The favorable effects on vascular endothelium could potentially lead to a decrease in vascular events.

Topics: Aged; Coronary Artery Disease; Dinoprost; Double-Blind Method; Endothelium, Vascular; Epoprostenol; Female; Forearm; Hemodynamics; Humans; Hyperemia; Male; Prospective Studies; Regional Blood Flow; Vasodilation; Vasodilator Agents

The inflammatory events related to prostaglandins may play an important role in the progression of vessel stenosis. The aim of this study was to investigate the monocyte PTGES and 15-PGDH gene expression levels and the serum 13,14-dihyro-15-keto-PGF2α value involved in PGE2 metabolism in patients with coronary artery stenosis and restenosis. Moreover, the effects of miR-520, miR-1297 and miR-34 were studied on the gene expression levels. A total of sixty subjects referred for coronary angiography including healthy controls (stenosis <5%), subjects with stent no restenosis) SNR, stenosis <5%) and subjects in stent restenosis (ISR, restenosis >70%) were participated in the study. The gene expression levels and the serum 13,14-dihyro-15-keto- PGF2α value were measured by RT-qPCR and ELISA techniques, respectively. Moreover, the effects of miRNAs on the gene expression levels were investigated by the monocyte transfection of miR/PEI complexes. The PTGES and 15-PGDH gene expression levels and serum 13,14-dihyro-15-keto- PGF2α value increased significantly (P <0.05). Based on the miR-520 and miR-34 expression levels, the miR/PEI transfection studies were confirmed significantly the gene expression changes. The monocyte PGE2 synthesis pathway is actively considered in the SNR and ISR patients and might be related to miR-34 and miR-520 functions.

Topics: Adult; Aged; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Stenosis; Dinoprost; Dinoprostone; Female; Gene Expression; Gene Expression Regulation; Humans; Hydroxyprostaglandin Dehydrogenases; Male; MicroRNAs; Middle Aged; Stents

Postprandial hyperglycemia was reported to play a key role in established risk factors of coronary artery diseases (CAD) and cardiovascular events. Serum 1,5-anhydroglucitol (1,5-AG) levels are known to be a clinical marker of short-term postprandial glucose (PPG) excursions. Low serum 1,5-AG levels have been associated with occurrence of CAD. However, the relationship between 1,5-AG levels and coronary plaque rupture has not been fully elucidated. The aim of this study was to evaluate 1,5-AG as a predictor of coronary plaque rupture in diabetic patients with acute coronary syndrome (ACS).. A total of 144 diabetic patients with ACS were included in this study. All patients underwent intravascular ultrasound examination, which revealed 49 patients with plaque rupture and 95 patients without plaque rupture in the culprit lesion. Fasting blood glucose (FBG), hemoglobin A. Serum 1,5-AG may identify high risk for coronary plaque rupture in diabetic patients with ACS, which suggests PPG excursions are related to the pathogenesis of plaque rupture in diabetes.

Topics: Acute Coronary Syndrome; Aged; Biomarkers; Blood Glucose; Coronary Artery Disease; Coronary Vessels; Deoxyglucose; Diabetes Mellitus, Type 2; Dinoprost; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Plaque, Atherosclerotic; Predictive Value of Tests; Prospective Studies; Rupture, Spontaneous; Ultrasonography, Interventional

Aspirin use is effective in the prevention of cardiovascular disease; however, not all patients are equally responsive to aspirin. Oxidative stress reflected by F2-isoprostane [8-iso-prostaglandin-F2α (8-IsoPGF2α)] is a potential mechanism of failure of aspirin to adequately inhibit cyclooxygenase-1. The objective was to examine the relation between all-cause mortality and the concentrations of urinary 11-dehydro thromboxane B2 (11dhTxB2) and 8-IsoPGF2α in patients with stable coronary artery disease (CAD).. The data for this analysis are from a prospective study in which patients were categorized into four groups based on the median values of 11dhTxB2 and 8-IsoPGF2α.. There were 447 patients included in this analysis with a median (range) age of 66 (37-91) years. The median (range) values of 11dhTxB2 and 8-IsoPGF2α were 1404.1 (344.2-68296.1) and 1477.9 (356.7-19256.3), respectively. A total of 67 (14.9%) patients died over a median follow-up of 1149 days. The reference group for the Cox proportional hazards survival analysis was patients with values of 11dhTxB2 and 8-IsoPGF2α below their corresponding medians. Adjusting for the age and sex, patients with values of 11dhTxB2 greater than the median had a significantly higher risk of mortality when compared with the reference group (high 11dhTxB2 and low 8-IsoPGF2αadj: hazard ratio: 3.2, 95% confidence interval: 1.6-6.6, P=0.002; high 11dhTxB2 and 8-IsoPGF2αadj: hazard ratio: 3.6, 95% confidence interval: 1.8-7.3, P<0.001). The findings were similar when we adjusted for the comorbidities of cancer, kidney function, and ejection fraction.. We found that 11dhTxB2 appears to be a better prognostic marker for mortality as compared with 8-IsoPGF2α, suggesting aspirin resistance itself is a stronger independent determinant of death in CAD patients treated with aspirin.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Biomarkers; Cause of Death; Coronary Artery Disease; Cyclooxygenase Inhibitors; Dinoprost; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Male; Middle Aged; Oxidative Stress; Prognosis; Prospective Studies; Risk Factors; Survival Rate; Texas; Thromboxane B2; Time Factors

The study was aimed to assess paraoxonase-1 (PON1) activity, pleiotropic effects of simvastatin, and its relationship to Q192R and M55L polymorphisms in obese and non-obese subjects with stable coronary artery disease (CAD).. The study included 53 subjects (22 obese) aged from 35 to 65 years with CAD. The control group consisted of 53 (18 obese) police officers without CAD. Patients with CAD were treated with simvastatin 40 mg/day for 12 months. The lipid profile, flow mediated dilation (FMD), intima media-thickness (IMT), fibrinogen, hs-CRP, TNF-α, urine 8-iso-PGF2α, and PON1 activity were evaluated in definite time points. PON1 polymorphisms were assessed at baseline in all observed individuals.. The patients with CAD and obesity presented at baseline significantly increased hs-CRP level, insignificantly decreased FMD and lower PON1 activity compared to non-obese individuals. There was no association of obesity with 8-iso-PGF2α in the CAD and control group. The PON1 activity was significantly higher in 192R carriers in patients and controls, irrespective of obesity. Obesity was not associated with the effects of simvastatin on PON1 activity, urine 8-iso-PGF2α, and TNF-α, whereas it blunted its effect on the FMD improvement. The Q192R polymorphism was associated with simvastatin effectiveness on hs-CRP and FMD.. Obesity and Q192R PON1 polymorphism are significantly associated with pleiotropic effects of simvastatin therapy in patients with stable CAD.

Topics: Adult; Aged; Aryldialkylphosphatase; C-Reactive Protein; Coronary Artery Disease; Dinoprost; Female; Humans; Male; Middle Aged; Obesity; Polymorphism, Single Nucleotide; Simvastatin; Tumor Necrosis Factor-alpha

Topics: Aged; Aspirin; Coronary Artery Disease; Cross-Sectional Studies; Cyclooxygenase 1; Dinoprost; F2-Isoprostanes; Female; Humans; Male; Middle Aged; Oxidative Stress; Platelet Aggregation Inhibitors; Thromboxane B2

The impact of systemic inflammation on clinical outcomes after CABG surgery is still controversial. In this study, we evaluated the impact of the markers of inflammation, endothelial damage and platelet activation on clinical outcomes after on- and off-pump CABG.. A group of 191 consecutive on- and off-pump CABG patients were prospectively studied. Blood samples were drawn before surgery, 18-36h after the procedure and 5-7 days postoperatively and analyzed for 8-iso-prostaglandin F. Elevation of 8-iso-PGF. Links between preoperative 8-iso-PGF

Topics: Aged; beta-Thromboglobulin; Biomarkers; C-Reactive Protein; Cardiopulmonary Bypass; Coronary Artery Bypass; Coronary Artery Disease; Dinoprost; Female; Follow-Up Studies; Hospital Mortality; Humans; Incidence; Inflammation; Male; Middle Aged; Poland; Postoperative Complications; Postoperative Period; Predictive Value of Tests; Preoperative Period; Prospective Studies; Survival Rate

The aim of the study was to estimate association of the extent of angiographically proven coronary artery disease (CAD) with plasma 8-isoprostane F2 (8-iso-PGF2α) levels as a reliable marker of lipid peroxidation and serum activity of paraoxonase-1, which demonstrates the ability to protect against lipid oxidation. The study included 105 patients with angiographically documented CAD (CAD+) and 45 patients with negative results of coronary angiography (CAD-). Compared to the control group CAD+ patients were characterized by increased 8-iso-PGF2α levels (P = 0.007) and reduced activity of PON-1 towards paraoxon (PONase, P = 0.002) and phenyl acetate (AREase, P = 0.037). Univariate correlation analysis indicated that 8-iso-PGF2α concentrations were positively associated with the severity of CAD as evaluated by the Gensini score (R = 0.41, P < 0.001) while PONase activity (R = -0.26, P < 0.05) and AREase activity (R = -0.23, P < 0.05) were inversely correlated with CAD severity. PONase activity and 8-iso-PGF2α concentration remained independent determinant of atherosclerosis severity in multiple linear regression after adjusting for age, gender, smoking habits, hypertension, type 2 diabetes, statin therapy, and HDL-C and TAG concentration (β coefficients -0.267; P < 0.05 and 0.368; P < 0.001, resp.). The results suggest that PON-1 activity and 8-iso-PGF2α concentration are associated with the presence and extent of coronary stenosis and may be considered additional markers of coronary artery disease.

Topics: Aged; Aryldialkylphosphatase; Carboxylic Ester Hydrolases; Cholesterol, HDL; Coronary Angiography; Coronary Artery Disease; Dinoprost; Female; Humans; Linear Models; Male; Middle Aged; Phenotype; Severity of Illness Index

Tobacco smoking is the leading atherosclerosis risk factor and substantially influences its pathophysiology.. The aim of this study was to assess the impact of tobacco smoking on paraoxonase-1 (PON1) activity and the relationship with pleiotropic effects of simvastatin therapy and PON1 gene polymorphisms.. 53 patients with stable coronary artery disease (CAD) and hypercholesterolemia were enrolled in the patients group (35 smokers) and 53 healthy controls (27 smokers). Individuals in the patients group were treated with simvastatin (40 mg) for 12 months. Markers of oxidative stress, inflammation, endothelial function and PON1 activity at baseline, after 6 and 12 months were evaluated in the patients group.. The baseline mean levels of serum high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNFα), plasma fibrinogen, urine 8-iso-prostaglandin F₂α (8-iso- PGF₂α), PON1 activity, flow-mediated dilation (FMD) and intima-media thickness (IMT) value did not significantly correlated with smoking habit in the patients and controls group. The significant decrease of hs-CRP (p = 0.017) and TNFα (p = 0.003) concentration after simvastatin was found in smokers, and 8-iso-PGF₂α in smokers and 192QQ allele carriers (p = 0.038). Whereas the FMD significantly improved only in the subgroup of non-smokers (p = 0.019) and 192QQ allele carriers (p = 0.049).. Smoking significantly modified pleiotropic effects of simvastatin on proinflammatory markers and endothelial function. No effect of simvastatin therapy and no correlation of smoking habit with PON1 activity could be affected by the distribution of PON1 polymorphism, concomitant diseases and their treatment, as well as relatively stable level of oxidative stress markers during the observational period.

Topics: Adult; Aged; Aryldialkylphosphatase; C-Reactive Protein; Coronary Artery Disease; Dinoprost; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Polymorphism, Genetic; Simvastatin; Smoking; Tumor Necrosis Factor-alpha

Oxidative stress has been implicated in the development of coronary artery calcification (CAC). However, there are few reports on this issue in Japanese patients with diabetes. In this study, we examined the association of the CAC score (CACS) with oxidative stress markers.. The study subjects were 163 Japanese patients with type 2 diabetes (75 men and 88 women). The CACS (Agatston unit: AU) was measured by multi-detector computed tomography (MDCT), and the oxidative stress markers, such as the urinary 8-isoprostane and 8-hydroxydeoxyguanosine (8-OHdG) and serum malondialdehyde (MDA)-LDL cholesterol were measured. The relationships between CACS and oxidative stress markers were statistically analyzed.. Compared with the CACS 0-400 AU group (n=132), the age, duration of diabetes, urinary 8-isoprostane levels, serum MDA-LDL-C/LDL-C and maximum intima media thickness (IMT) were higher, and body mass index and HbA1c level were lower, in the CACS >400 AU group (n=31). The multiple logistic regression analysis showed that a CAC >400 AU was independently associated with the urinary 8-isoprostane (>median) (OR=2.54, 95% CI=1.03-6.32, p=0.044), MDA-LDL-C/LDL-C (>median) (OR=2.62, 95% CI=1.07-6.40, p=0.035) and HbA1c (>median) (OR=0.32, CI=0.12-0.87, p<0.025). Focusing on oxidative stress, a higher MDA-LDL-C/LDL-C (p=0.026) and a higher urinary 8-isoprostane level (p=0.074) were associated with the CACS.. The CACS was found to be independently associated with the MDA-LDL-C/LDL-C and urinary 8-isoprostane levels in Japanese patients with type 2 diabetes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Calcinosis; Carotid Intima-Media Thickness; Cholesterol, LDL; Coronary Artery Disease; Diabetes Mellitus, Type 2; Dinoprost; Female; Follow-Up Studies; Humans; Incidence; Japan; Male; Malondialdehyde; Middle Aged; Multidetector Computed Tomography; Oxidative Stress; Prevalence; Retrospective Studies; Tomography, X-Ray Computed; Young Adult

Although oxidative stress (OxS) is thought to contribute to atherosclerosis and coronary artery disease (CAD), little is known about the variability in an individual's ability to respond to OxS. Therefore, we assessed potential indices of response to OxS and evaluated whether they modify the association between OxS and CAD.. We evaluated plasma α- and γ-tocopherol per unit cholesterol (potential response markers); urinary 15-isoprostane F2t per milligram creatinine (isoprostane [IsoP], a potential stress marker); and the α-tocopherol-to-IsoP ratio (as a measure of response to stress), measured three times during 20 years of follow-up, in relation to CAD incidence in a cohort with childhood-onset type 1 diabetes (n = 658; mean age at baseline, 28 years; duration of diabetes, 19 years). Participants with three samples (blood and either 24-h or overnight urine) available before the onset of CAD or the end of follow-up (n = 356) were selected for study.. In multivariable mixed models, α-tocopherol over time was inversely associated with CAD (β = -0.27; P = 0.02), whereas a direct association was observed for IsoP (β = 0.0008; P = 0.06). Moreover, the α-tocopherol-to-IsoP ratio was strongly and inversely related to CAD incidence (β = -0.72; P = 0.003), whereas in a separate model including α-tocopherol and IsoP, both biomarkers maintained statistical significance. No association was observed for γ-tocopherol (β = -0.22; P = 0.54).. These data suggest that a greater potential capability (α-tocopherol) to respond to OxS (urinary IsoP) relates to CAD incidence.

Topics: Adult; alpha-Tocopherol; Biomarkers; Coronary Artery Disease; Creatinine; Diabetes Mellitus, Type 1; Dinoprost; Female; Humans; Incidence; Isoprostanes; Male; Oxidative Stress; Young Adult

It remains unclear whether atherosclerosis in one vascular bed progresses in parallel with that in other vascular beds. We investigated serial changes in vessel wall areas (VWAs) in various vessels over 2 years of follow-up. Vessel wall areas in the thoracic descending aorta (TDA), common carotid artery (CCA), right (RCA), and left main trunk (LMT) of coronary artery were determined in 52 patients with coronary artery disease (CAD) using 64-slice multidetector computed tomography. Plasma levels of high-sensitivity CRP (hs-CRP) and matrix metalloproteinase (MMP)-9, as well as urinary 8-iso-prostaglandin F2α (PGF2α) were determined at the baseline. After the follow-up period, plaque progression in a specific vessel did not parallel that of other vessels, although changes in TDA-VWAs were weakly correlated with those of LMT-VWAs. Basal levels of hs-CRP, MMP-9, and PGF2α did not predict progression or regression of VWAs in any vessels. Multivariate analyses showed that LDL-cholesterol < 100 mg/dl and use of statin emerged as predictors of regressing VWAs in TDA (p < 0.05 and p < 0.05, respectively) and LMT (p < 0.05 and p = 0.13, respectively). Changes in soft plaques over 2 years paralleled those of VWAs in both coronary arteries. In conclusion, the progression or regression of atherosclerotic plaques is inhomogeneous among the vascular beds of patients with CAD.

Topics: Aged; Aorta, Thoracic; Aortic Diseases; Aortography; Atherosclerosis; Biomarkers; C-Reactive Protein; Carotid Artery Diseases; Carotid Artery, Common; Cholesterol, LDL; Coronary Angiography; Coronary Artery Disease; Dinoprost; Disease Progression; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Logistic Models; Male; Matrix Metalloproteinase 9; Middle Aged; Time Factors; Tomography, X-Ray Computed

Both statins and renin-angiotensin system (RAS) inhibitors inhibit atherosclerotic progression and reduce cardiovascular events. However, it remains unclear whether combination therapy of RAS inhibitor with statin could inhibit plaque progression more than statin alone.. Using 64 multislice computed tomography, vessel wall areas (VWAs) and total vascular areas of the left main trunk (LMT) and proximal right coronary artery (RCA) and the thoracic descending aorta (TDA) were determined in patients with coronary artery disease before and after 2.0-year treatment with atorvastatin and candesartan (n=20) or with atorvastatin alone (n=16), although these patients had been treated with the combination therapy or statin alone at the study enrollment. Plasma levels of high sensitive C-reactive protein, matrix metalloproteinase-9, and urinary 8-iso-prostaglandin F2α were determined at the baseline.. There were no significant differences in low-density lipoprotein and high-density lipoprotein cholesterol, C-reactive protein, matrix metalloproteinase-9, or urinary 8-iso-prostaglandin F2α levels between the two groups. Two years later, total vascular areas of TDA and RCA increased significantly in the atorvastatin group but not in the combination group. Moreover, increases in VWAs were less in the combination group than in the atorvastatin group in TDA (3.6 ± 23.1 vs. 28.6 ± 25.5 mm, P=0.004), RCA (-1.6 ±1.6 vs. 0.6 ± 2.5 mm, P=0.005), and left main trunk (-0.9 ± 3.5 vs. 1.3 ± 2.4 mm, P=0.095). Biomarker levels at the baseline did not affect the progression of VWA.. Combination therapy of RAS inhibitor with statin is more effective than statin alone in inhibiting atherosclerotic progression of coronary arteries and the aorta in patients with coronary artery disease.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Anticholesteremic Agents; Atherosclerosis; Atorvastatin; Benzimidazoles; Biomarkers; Biphenyl Compounds; C-Reactive Protein; Cholesterol; Coronary Artery Disease; Dinoprost; Disease Progression; Drug Therapy, Combination; Female; Follow-Up Studies; Heptanoic Acids; Humans; Longitudinal Studies; Male; Matrix Metalloproteinase 9; Middle Aged; Pyrroles; Tetrazoles; Tomography, X-Ray Computed

Several patient characteristics have been shown to increase the risk of inadequate platelet inhibition by aspirin, yet underlying mechanisms remain mostly unknown. We explored whether oxidative stress, via isoprostane formation, was associated with inadequate platelet response to aspirin. Additionally, we sought to investigate whether individual pre-selected demographic, hematological or biochemical parameters further increased the risk of inadequate platelet response to aspirin.. Two hundred consecutive subjects suffering from stable coronary artery disease and under daily aspirin therapy were enrolled in our study. Inadequate platelet response to aspirin was defined as residual platelet aggregation>or=20% per arachidonic acid-induced light transmission aggregometry. Morning urinary samples were used to determine levels of isoprostanes (8-iso-PGF2alpha) using an enzyme immunoassay.. Eight subjects were deemed to present inadequate platelet response to aspirin. Wide intersubject variability was observed in urinary 8-iso-PGF2alpha levels. However, levels were similar between aspirin responders and non-responders. Patients with inadequate platelet response to aspirin had higher platelet counts and received the lowest daily aspirin dose when compared to responders, suggesting subtherapeutic aspirin therapy due to increased platelet production. Only platelet count remained independently predictive of inadequate platelet response to aspirin in a multiple logistic regression model.. Urinary 8-iso-PGF2alpha levels, a reflection of systemic oxidative stress, did not appear to contribute to impaired platelet responsiveness to aspirin, while increased platelet production may partly explain this phenomenon.

Topics: Aged; Aspirin; Blood Platelets; Coronary Artery Disease; Dinoprost; Drug Resistance; Female; Humans; Male; Middle Aged; Oxidative Stress; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Count; Risk Factors; Thromboembolism; Treatment Failure

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

Matrix metalloproteinase (MMP), which is activated by oxidative stress, plays an important role in the development of ventricular remodeling in coronary artery disease. Pravastatin is shown to reduce oxidative stress. We tested the hypothesis that cardiac oxidative stress and MMP activity are reduced in patients with coronary artery disease and treated with pravastatin. Forty-eight patients who underwent coronary artery bypass graft surgery (CABG) were studied. Twenty-four patients had the serum low-density lipoprotein (LDL) cholesterol level >2.59 mM, and were treated with pravastatin (10 mg/day) for 2 months before CABG (pravastatin group). The other 24 had LDL cholesterol< or =2.59 mM, and were untreated (control group). The plasma and pericardial MMP-2 and MMP-9 activities were measured by gelatin zymography, and MMP-2 and MMP-9 levels, and pericardial 8-iso-prostagrandin F2alpha (8-iso-PGF2alpha) level, a maker of oxidative stress, by enzyme-linked immunosorbent assay. The plasma and pericardial MMP-2 and MMP-9 activities and levels were all lower by 20-30% in pravastatin than in control group (all P<0.05). The pericardial 8-iso-PGF2alpha level was lower in pravastatin than in control group (38+/-4 vs 64+/-7 pg/ml, P<0.05). The pericardial MMP-2 and MMP-9 activities were positively correlated with the pericardial 8-iso-PGF2alpha level (r=0.57 and 0.47, respectively, both P<0.01). Thus, cardiac oxidative stress and MMP activities are reduced in patients with coronary artery disease and treated with pravastatin, which may be beneficial in preventing and reducing ventricular remodeling.

Topics: Aged; Coronary Angiography; Coronary Artery Bypass; Coronary Artery Disease; Dinoprost; Electrophoresis, Polyacrylamide Gel; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Middle Aged; Myocardium; Oxidative Stress; Pericardial Effusion; Pravastatin

Atherosclerotic coronary artery disease is the leading cause of death worldwide. Oxidative stress is one of the key elements in the pathogenesis of atherosclerosis. Isoprostanes are established markers of oxidative stress. The aim of this study was to investigate the association of urinary 8-isoprostane levels with the presence and severity of coronary artery disease (CAD) assessed by a validated scoring system.. Urinary 8-isoprostane levels were measured in 100 consecutive patients scheduled for coronary angiography. Extent and severity of CAD were assessed by modified Gensini scores.. In patients with CAD, 8-isoprostane levels were higher (P < 0.001) than in patients without CAD (68.75 +/- 5.5 vs. 38.27 +/- 3.7 pg/ml). The levels of 8-isoprostane correlated with the number of risk factors (P < 0.001) and significantly increased in relation with the number of diseased vessels (P < 0.001). A significant (P < 0.001) correlation was found between 8-isoprostane levels and Gensini scores (r = 0.496), and a stepwise elevation in 8-isoprostane levels was observed across the increasing tertiles of the Gensini scores (P < 0.001). The multivariate logistic regression analysis revealed that 8-isoprostane was an independent predictor (odds ratio: 7.19 and P = 0.007) associated with angiographic CAD.. These results confirm the role of oxidative stress in the atherosclerotic process. Urinary 8-isoprostane levels reflect the extent and severity of CAD and they may provide additional information for risk assessment in patients with suspected CAD.

Topics: Biomarkers; C-Reactive Protein; Case-Control Studies; Coronary Angiography; Coronary Artery Disease; Dinoprost; Female; Health Status Indicators; Humans; Inflammation; Logistic Models; Male; Middle Aged; Oxidative Stress; Risk Factors; Severity of Illness Index

Oxidative stress has been implicated in the pathogenesis of atherogenesis. The aim of our study is to examine whether the plasma 8-iso-prostaglandin F(2alpha) level, a marker of oxidative stress, is elevated in patients with acute myocardial infarction.. Three groups of patients were enrolled: (1) patients with no or minimal coronary artery disease (CAD) (n = 15); (2) patients with stable CAD (n = 31); (3) patients with acute myocardial infarction (n = 13).. Plasma 8-iso-prostaglandin F(2alpha) levels were significantly elevated (p < 0.001) in patients with acute myocardial infarction (290.7 +/- 73.9 pg/ml) as compared to patients with stable CAD (182.0+75.7 pg/ml) and patients with no significant CAD (118.9 +/- 85.5 pg/ml). This remained significant after correcting for coronary atherosclerosis risk factors, age, extent of atherosclerosis, and C-reactive protein (CRP) level.. Plasma 8-iso-prostaglandin F(2alpha) levels are elevated in patients with acute myocardial infarction. Endogenous oxidative stress may contribute to the pathogenesis of atherosclerosis and its complications, namely myocardial infarction.

Topics: Acute Disease; Biomarkers; Coronary Artery Disease; Dinoprost; Female; Humans; Male; Middle Aged; Myocardial Infarction; Oxidative Stress; Risk Factors

Aspirin resistance (AR) is estimated to be present in 5-75% of patients and is related to increased cardiovascular mortality. However, the underlying mechanisms are mostly unknown. In the present study, AR was detected in 14 out of 55 patients (25%) with coronary artery disease. The presence of concomitant anti-inflammatory drugs did not affect AR. Plasma levels of thromboxane B(2) as well as the markers for oxidative stress and known platelet activators 8-isoprostane and lipid peroxidation products were significantly higher in aspirin-resistant individuals (349.3 pg/ml, 53.9 pg/ml, and 538 micromol/l) compared to controls (113.7 pg/ml, 10.3 pg/ml, and 32.2 micromol/l; P < 0.05, respectively). Platelet cyclooxygenase-1 (COX-1) and COX-2 mRNA and protein expression were without significant differences between the two groups. DNA sequencing detected a novel platelet COX-1 single nucleotide polymorphism (SNP) resulting in amino acid exchange at position 8 (Arg8/Trp8). The wild-type as well as the heterozygous and homozygous SNP were present in both patient groups without significant differences. The aspirin binding (Arg120) and acetylation site (Ser529) were unaffected in the samples tested. Neither was AR related to the platelet integrin PlA(1)/A(2) polymorphism. In conclusion, AR appears to be unrelated to differences in platelet COX-1 and COX-2 expression or to a novel platelet COX-1 SNP and the PlA(1)/A(2) SNP. However, a correlation exists to elevated eicosanoids generated by oxidative stress indicating COX-1-independent pathways for the generation of platelet activating molecules represent a potential cause for AR.

Topics: Antigens, Neoplasm; Aspirin; Blood Platelets; Coronary Artery Disease; Cyclooxygenase 1; Dinoprost; Drug Resistance; Humans; Integrin beta3; Lipid Peroxidation; Nephelometry and Turbidimetry; Oxidative Stress; Platelet Aggregation; Polymorphism, Genetic; Polymorphism, Single Nucleotide; RNA, Messenger; Thromboxane A2; Thromboxane B2

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Coronary Artery Disease; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprost; Humans; Isoenzymes; Membrane Proteins; Platelet Aggregation Inhibitors; Prostaglandin-Endoperoxide Synthases; Sulfonamides; Thromboxane A2

Topics: Arteriosclerosis; Carotid Artery Diseases; Coronary Artery Disease; Dinoprost; Humans; Lipid Peroxidation; Logistic Models; Lupus Erythematosus, Systemic; Oxidative Stress; Tumor Necrosis Factor-alpha

We sought to study circulating levels of pro- and anti-inflammatory cytokines together with the oxygen stress index in patients with chronic heart failure (CHF).. Patients with CHF exhibit elevated levels of inflammatory and anti-inflammatory cytokines but the relative level of these cytokines with the oxygen stress index have not been reported.. Twenty-two patients with CHF and 10 control subjects were studied. Plasma levels of IL-6 and IL-10 were determined and the oxygen stress index was evaluated by urine 8-iso-PGF2alpha estimations.. Plasma levels of IL-6 and IL-10 in CHF patients were significantly higher than those observed in the control subjects. Patients with more advanced disease (higher NYHA class) showed higher concentrations of IL-10 and IL-6 than those with less serious disease. 8-iso-PGF2alpha urine concentration (and therefore the oxygen stress index) was significantly higher in patients with CHF in comparison with control subjects. IL-6 plasma levels, but not IL-10 concentrations, correlated significantly with 8-iso-PGF2alpha levels in urine.. Inflammatory and anti-inflammatory cytokine levels, as well as the oxidative stress index, are increased in patients with chronic heart failure. Inflammatory cytokine IL-6, but not anti-inflammatory cytokine Il-10, levels correlated significantly with the oxygen stress index.

Topics: Aged; Cardiomyopathy, Dilated; Coronary Artery Disease; Dinoprost; Female; Heart Failure; Humans; Interleukin-10; Interleukin-6; Male; Middle Aged; Oxidative Stress

It is well known that free radicals contribute to endothelial dysfunction and are involved in the pathogenesis and development of cardiovascular diseases, such as atherosclerosis. The aim of this study was to provide evidence for enhanced oxidative stress in coronary artery disease (CAD).. Plasma levels of 8-isoprostane (8-epiPGF(2alpha)), marker of lipid peroxidation, were measured in 68 subjects (age: 60 +/- 2 years, mean +/- SEM). Subjects included 30 healthy control subjects and 38 patients with angiographically proven CAD. In addition, the total antioxidant power (PAO) was evaluated in a subgroup (40 subjects, 12 healthy and 28 CAD).. Levels of 8-epiPGF(2alpha) increased with the number of affected vessels (one- and multi-vessel disease versus control subjects, P < 0.001) and considering different risk determinants for atherosclerosis (i.e. hypertension, gender, hypercholesterolaemia, P < 0.01). In multivariate regression models the number of affected vessels was independently correlated with 8-epiPGF(2alpha) (P < 0.05). PAO values significantly decreased with increased number of affected vessels (P < 0.05) and in hypertensive patients when compared with those without hypertension (P < 0.05). In multivariate regression models the number of affected vessels resulted an independent determinant for PAO (P < 0.05). Concentration of 8-epiPGF(2alpha) and PAO also correlated with the number of cardiovascular risk factors (P < 0.01 and P = 0.07, respectively).. These findings indicate that elevated levels of plasma 8-epiPGF(2alpha) and reduced antioxidant capacity are associated with the extent and the severity of CAD and with the occurrence and number of different atherogenic risk factors. This observation may assist in providing more information as to how oxidative stress may predispose to atherogenesis and suggest attractive therapeutic strategies in the prevention and treatment of cardiovascular disease.

Topics: Antioxidants; Biomarkers; Coronary Artery Disease; Dinoprost; Female; Humans; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Risk Factors

It is well known that free radicals contribute to endothelial dysfunction and are involved in ageing and in the pathogenesis and development of many cardiovascular diseases, such as atherosclerosis. Measurement of F(2)-isoprostanes has emerged as probably the most reliable approach to assess oxidative stress status in vivo. In particular, 8-isoprostane (8-epiPGF(2alpha)) has been indicated as a marker of antioxidant deficiency and oxidative stress of potential relevance to assess human vascular diseases.. To provide evidence for enhanced oxidative stress in coronary artery disease (CAD).. Plasma levels of 8-epiPGF(2alpha) (EIA, Cayman Chemicals, Ann Arbor, Michigan, USA) were measured in 51 patients (19 females, 32 males, age: 58.7+/-1.6 years, mean+/-SEM). Subjects included 13 healthy control subjects (group I), and 38 patients underwent coronary angiography; 11 patients without coronary artery atherosclerotic lesions (group II), and 27 with angiographically proven CAD (group III).. Plasma levels of 8-epiPGF(2alpha) were 123.2+/-9.5, 314.6+/-40 and 389.6+/-36.2 pg/ml in groups I, II and III respectively (P<0.05 and P<0.001 groups II and III versus group I, respectively). In group III, 8-epiPGF(2alpha) levels increased with the number of affected vessels (324.4+/-47.2 and 408.3+/-44.1 pg/ml for one- and multi-vessel disease, P=0.07 and P<0.001 versus control subjects, respectively). A significant difference in 8-epiPGF(2alpha) levels was observed between patients with and without hypertension (394.2+/-42.7 and 232.7+/-25.1 pg/ml, P<0.01, respectively). In addition, patients with dyslipidaemia presented higher 8-epiPGF(2alpha) levels with respect to non-dyslipidaemic patients (359.1+/-35.6 and 240.3+/-34.3 pg/ml, P<0.05, respectively). A positive relationship was found between age and 8-epiPGF(2alpha) levels (r=0.42, P<0.01) in the whole population.. These findings indicate that elevated levels of plasma 8-epiPGF(2alpha) levels are associated with the extent and the severity of coronary artery disease and with the occurrence of different atherogenic risk factors, supporting the hypothesis that the evaluation of oxidative stress may represent an additional prognostic predictor in such events and a potential target of future therapeutic interventions.

Topics: Aged; Biomarkers; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Dinoprost; Evidence-Based Medicine; F2-Isoprostanes; Female; Humans; Hyperlipidemias; Hypertension; Italy; Male; Middle Aged; Oxidative Stress; Regression Analysis; Risk Factors; Smoking; Statistics as Topic

Coronary risk factors, including age, hypertension, diabetes mellitus, hyperlipidemia, and smoking, are associated with enhanced oxidative stress, which is implicated as a potential mechanism for atherogenesis and atherosclerotic cardiovascular diseases. Male sex is one of the well-known cardiovascular risk factors. We tested the hypothesis that oxidative stress is greater in men than in women. Plasma thiobarbituric acid-reactive substances (TBARS) and urinary 8-isoprostaglandin F2alpha (8-iso-PGF2alpha) were measured in 52 young men and 51 age-matched women. The subjects were healthy, were not smokers, and were not taking any medications or vitamins. Age, blood pressure, plasma cholesterol, and glucose did not differ between the groups. Baseline TBARS (2.32 +/- 0.11 [men] versus 1.87 +/- 0.09 [women] nmol/mL, P<0.01) and 8-iso-PGF2alpha (292 +/- 56 [men] versus 164 +/- 25 [women] pg/mg creatinine, P<0.05) were higher in men than in women. Supplementation of antioxidant vitamins for 4 weeks in men produced a significant reduction in TBARS and 8-iso-PGF2alpha by 34% (P<0.01) and 48% (P<0.05), respectively. Plasma superoxide dismutase, catalase, and vitamin E levels were comparable between the groups. Enhanced oxidative stress in men may provide a biochemical link between male sex and atherosclerotic diseases related to oxidative stress.

Topics: Adult; alpha-Tocopherol; Antioxidants; Catalase; Coronary Artery Disease; Dinoprost; Estrogens; F2-Isoprostanes; Female; Humans; Male; Oxidative Stress; Premenopause; Sex Factors; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vitamin D

Oxidation of lipids is considered a key feature of atherogenesis. Lipid peroxidation products such as oxidized LDL or the bioactive aldehyde 4-hydroxynonenal (HNE) exert mitogenic effects on vascular smooth muscle cells (VSMC). These effects appear to be concentration-dependent since in addition to our previous reports on growth promotion at lower concentrations we here indicate induction of apoptosis in VSMC by 4-hydroxynonenal (HNE) at higher concentrations (100 micromol/L). In a line with HNE's previously documented effects on key mitogenic signaling elements, we also report on activation by this aldehyde of the redox-sensitive transcription factor NF-kappaB, a key regulator of apoptosis: HNE (1.0 micromol/L) induced DNA-binding of NF-kappaB in VSMC. The effect was inhibited by antioxidants, N-acetylcysteine and pyrrolidine dithio-carbamate. HNE caused phosphorylation but not degradation of the inhibitory subunit IkappaB-alpha. HNE itself acts as an oxidant as was investigated with measurements of 8-isoprostane which ranks among the most valuable available biomarkers of lipid peroxidation: HNE (1.0 micromol/L) increased 8-isoprostane levels in VSMC by 4.5-fold (p < 0.05). Compared to the controls, plasma samples from apoEnull mice exhibited elevated levels of 8-isoprostane (40 pg/mL, 3.2-fold increase) and the combined aldehydes HNE and malonaldehyde (1.5 micromol/L, 2.5-fold increase), (p < 0.05, resp). In addition, immunohistochemistry indicated the presence of HNE-protein adducts in atheroscerlotic lesions of apoEnull mice. Thus HNE is present in atherosclerotic tissue at concentrations that are bioactive in vitro. The data further indicate the involvement of the lipid peroxidation product HNE in atherogenesis.

Topics: Aldehydes; Animals; Aorta; Apolipoproteins E; Apoptosis; Cells, Cultured; Coronary Artery Disease; Culture Media, Conditioned; Cysteine Proteinase Inhibitors; Dinoprost; DNA; DNA-Binding Proteins; Dose-Response Relationship, Drug; F2-Isoprostanes; Humans; I-kappa B Proteins; Lipid Peroxidation; Lipid Peroxides; Mice; Mice, Knockout; Muscle, Smooth, Vascular; NF-kappa B; NF-KappaB Inhibitor alpha; Oxidative Stress; Phosphorylation; Proto-Oncogene Proteins c-bcl-2

Alteration of coronary vascular regulation during acute rejection may induce graft dysfunction and promote the occurrence of coronary atherosclerosis in transplant recipients. We studied the effects of treated and untreated acute rejection on coronary vascular regulation.. Two groups of mongrel dogs (n = 7) underwent heterotopic heart transplantation (cervical position) and received either no treatment (group 1) or cyclosporin A (CyA), 10 mg.kg-1.day-1 (group 2). On day 7, recipient native and transplanted hearts were harvested and studied in organ chambers for coronary vascular reactivity.. Transplanted hearts from group 1 displayed grade IV histologic rejection, whereas those from group 2 displayed grade IIIA to IV rejection. Intimal hyperplasia was found in the coronary arteries of both groups. Immunoperoxidase staining revealed the presence of factor VIII and of immunoglobulin M and G antibodies on the endothelium of both groups. Coronary relaxation to thrombin was impaired in transplanted hearts compared with native hearts (p < 0.05), and this was not influenced by CyA treatment. Conversely, endothelium-dependent relaxation to 5-hydroxytryptamine was enhanced in both CyA-treated (p < 0.01) and untreated groups (p < 0.05). A facilitating effect of CyA on 5-hydroxytryptamine also was seen in transplanted hearts in group 1 versus group 2 (p < 0.05), suggesting an intrinsic effect of CyA. Endothelium-independent relaxation to sodium nitroprusside and the contractile response to prostaglandin F2 alpha were not affected.. In our model, acute rejection did not specifically impair cyclic guanosine monophosphate-mediated relaxation, but it did affect, in a receptor-specific manner, endothelium-dependent relaxation. Cyclosporin A appeared to enhance coronary endothelial sensitivity to 5-hydroxytryptamine.

Topics: Acetylcholine; Acute Disease; Adenosine Diphosphate; Animals; Coronary Artery Disease; Coronary Circulation; Coronary Vessels; Cyclosporine; Dinoprost; Dogs; Dose-Response Relationship, Drug; Endothelium, Vascular; Factor VIII; Graft Rejection; Heart Transplantation; Immunoenzyme Techniques; Immunoglobulin G; Immunoglobulin M; Immunosuppressive Agents; In Vitro Techniques; Muscle, Smooth, Vascular; Myocardium; Nitroprusside; Serotonin; Thrombin; Transplantation, Heterotopic; Tunica Intima; Vasoconstriction; Vasodilation

Constriction of epicardial coronary arteries induces severe flow reduction causing myocardial ischaemia in patients with vasospastic angina. Whether such constriction is inherent in coronary arteries in general was determined by perfusing isolated epicardial coronary segments of humans and pigs at a constant perfusion pressure. Mean flow reduction after perfusion with potassium chloride (60 mmol.litre-1), acetylcholine (10(-9)-10(-5) mol.litre-1), and histamine (10(-8)-10(-4) mol.litre-1) was not different between humans and pigs. Prostaglandin F2 alpha (PGF2 alpha; 3 X 10(-6) mol.litre-1) decreased the flow more substantially in humans (by 74(9)%) than in pigs (by 6(1)%) (p less than 0.01). A pronounced flow reduction to 0 ml.min-1 was observed in eight of 17 human coronary arteries after potassium chloride, histamine, or PGF2 alpha perfusion but in none of the pigs. Histological examination of the coronary arteries showed no atherosclerotic lesions in the pigs but various lesions in humans, ranging from intimal thickening to 96% luminal stenosis in cross sectional area. Flow reduction after PGF2 alpha was significantly greater in human coronary arteries with stenoses greater than 50% (94(4)%) than in those with stenoses less than 25% (55(14)%) (p less than 0.05). Complete cessation of flow was observed more often in the stenotic arteries (greater than 50% stenosis) than in others (p less than 0.05). A substantial reduction in flow, which may cause myocardial ischaemia in vivo, was not seen in normal pig coronary arteries even after strong vasoconstrictor stimuli but was present in human coronary arteries with atherosclerosis.

Topics: Acetylcholine; Adult; Aged; Animals; Blood Flow Velocity; Coronary Artery Disease; Coronary Vessels; Dinoprost; Female; Histamine; Humans; In Vitro Techniques; Male; Middle Aged; Potassium Chloride; Swine; Vascular Resistance; Vasoconstrictor Agents

The prostanoid status was assessed in 138 patients with coronary atherosclerosis and clinical signs of stable angina. Plasma prostaglandin F2 alpha and E1, and stable prostacyclin and thromboxane metabolites were measured radioimmunologically, using standard kits. A relationship is demonstrated between the severity of clinical manifestations, and pattern and magnitude of change in individual prostanoids.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Alprostadil; Coronary Artery Disease; Dinoprost; Dinoprostone; Female; Humans; Male; Middle Aged; Prostaglandins E; Prostaglandins F; Thromboxane B2

Some indices of T and B cellular immunity and content of PgE2 and PgF2 alpha in the peripheral blood plasma were studied in 70 patients with coronary heart disease and in 22 patients with rheumatic disease complicated by chronic cardiac failure. It was revealed that increase in PgE2 and PgF2 alpha levels was accompanied by changes in T cells subpopulations. It is suggested that Pg-s can mediate changes of immunoregulatory lymphocyte functions in chronic cardiac insufficiency.

Topics: Adult; Aged; B-Lymphocytes; Chronic Disease; Coronary Artery Disease; Dinoprost; Dinoprostone; Female; Heart Failure; Humans; Immunity, Cellular; Male; Middle Aged; Prostaglandins E; Prostaglandins F; Rheumatic Heart Disease; T-Lymphocytes