11-dehydro-thromboxane-b2 and Arteriosclerosis

This trial evaluated the effect of antioxidant supplementation on the urinary excretion of 11-dehydro TXB(2)/2,3 dinor 6 keto PGF(1alpha) ratio, a marker of the pathogenesis of thrombosis and arteriosclerosis.. This study was a randomised, double-blind, placebo-controlled trial involving 186 presumably healthy volunteers. One hundred received a multi-antioxidant supplementation and 86 a placebo for two years. Blood zinc, selenium, beta-carotene, vitamin C and E and urinary excretion of 11-dehydro TXB(2) and 2,3 dinor 6 keto PGF(1alpha) were measured.. Baseline subject characteristics did not differ between the two groups. Blood zinc, selenium, and beta-carotene concentrations significantly increased between baseline and two years in the multi-antioxidant supplementation group supporting subject compliance (p < 0.05). At two years, the median urinary 11-dehydro TXB(2)/2,3 dinor 6 keto PGF(1alpha) ratio was significantly lower in the multi-antioxidant supplementation group (3.4 versus 2.78, p = 0.015). Serum selenium concentration was the only antioxidant studied that was significantly related to the urinary 11-dehydro TXB(2)/2,3 dinor 6 keto PGF(1alpha) ratio.. These results support the hypothesis that a low-dose multi-antioxidant supplementation may contributes to a reduction in platelet activation which is beneficial for cardiovascular function.

Topics: 6-Ketoprostaglandin F1 alpha; Antioxidants; Arteriosclerosis; beta Carotene; Biomarkers; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Patient Compliance; Platelet Activation; Prostaglandins I; Selenium; Thrombosis; Thromboxane B2; Thromboxanes; Trace Elements; Vitamins; Zinc

To investigate the effect of dietary saturated fat (SFA) from animal sources on the urine excretion 11-dehydro thromboxane B2 (TXB2) and 6-keto prostaglandin F 1alpha (PGF 1alpha) in 27 healthy free-living male subjects aged 30 to 55 years.. It was a randomized crossover design. Each volunteer was randomly assigned to one of the two diets (high fat and low fat) for a period of 4 weeks, after which each subject resumed his usual diet for 2 weeks as a 'wash-out period', before being assigned to the other diet for an additional 4 weeks.. Serum proportion of 20:4n-6 was 5% lower in the high fat (6.2% of total fatty acid) than in the low fat diet (6.5% of total fatty acid), which was associated with a significantly decreased ratio of the urinary excretion 11-dehydro TXB2 to 6-keto PGF 1alpha (P < 0.05). However, there was no significant fall in the absolute urinary excretion of 11-dehydro TXB2.. Diet rich in SFA from animal sources may influence TXA2 formation via effect on tissue proportion of 20:4n-6.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Arteriosclerosis; Cross-Over Studies; Dietary Fats; Fatty Acids; Humans; Male; Middle Aged; Thrombosis; Thromboxane B2

The formation of prostacyclin (PGI(2)), thromboxane (TX) A(2), and isoprostanes is markedly enhanced in atherosclerosis. We examined the relative contribution of cyclooxygenase (COX)-1 and -2 to the generation of these eicosanoids in patients with atherosclerosis.. The study population consisted of 42 patients with atherosclerosis who were undergoing surgical revascularization. COX-2 mRNA was detected in areas of atherosclerosis but not in normal blood vessel walls, and there was evidence of COX-1 induction. The use of immunohistochemical studies localized the COX-2 to proliferating vascular smooth muscle cells and macrophages. Twenty-four patients who did not previously receive aspirin were randomized to receive either no treatment or nimesulide at 24 hours before surgery and then for 3 days. Eighteen patients who were receiving aspirin were continued on a protocol of either aspirin alone or a combination of aspirin and nimesulide. Urinary levels of 11-dehydro-TXB(2) and 2,3-dinor-6-keto-PGF(1alpha), metabolites of TXA(2) and PGI(2), respectively, were elevated in patients with atherosclerosis compared with normal subjects (3211+/-533 versus 679+/-63 pg/mg creatinine, P<0.001; 594+/-156 versus 130+/-22 pg/mg creatinine, P<0.05, respectively), as was the level of the isoprostane 8-iso-PGF(2alpha). Nimesulide reduced 2, 3-dinor-6-keto-PGF(1alpha) excretion by 46+/-5% (378.3+/-103 to 167+/-37 pg/mg creatinine, P<0.01) preoperatively and blunted the increase after surgery. Nimesulide had no significant effect on 11-dehydro-TXB(2) before (2678+/-694 to 2110+/-282 pg/mg creatinine) or after surgery. The levels of both products were lower in patients who were taking aspirin, and no further reduction was seen with the addition of nimesulide. None of the treatments influenced urinary 8-iso-PGF(2alpha) excretion.. Both COX-1 and -2 are expressed and contribute to the increase in PGI(2) in patients with atherosclerosis, whereas TXA(2) is generated by COX-1.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arteriosclerosis; Aspirin; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprost; Epoprostenol; F2-Isoprostanes; Female; Humans; Isoenzymes; Macrophages; Male; Membrane Proteins; Microscopy, Fluorescence; Muscle, Smooth, Vascular; Prostaglandin-Endoperoxide Synthases; Sulfonamides; Thromboxane A2; Thromboxane B2

This study investigates how strenuous arm exercise affects oxidized-low density lipoprotein (O(X)-LDL) mediated-platelet activation in patients with SCI. Ten patients with SCI and ten age- and sex-matched healthy subjects exercised strenuously using an arm crank ergometer. The following measurements were taken both when the subjects were at rest, and immediately after exercise: plasma lipid profile, O(X)-LDL mediated platelet aggregability and [Ca(2+)]i, urinary 11-dehydro-thromboxane B2 (11-dehydro-TXB2) and 8-iso-prostaglandin F(2alpha), (8-iso-PG F(2alpha)) contents, and plasma NO metabolite (nitrite plus nitrate) level. Based on these measurements, the major findings of this study can be summarized as follows: 1) the SCI group had higher urinary 8-iso-PGF(2alpha) and 11-dehydro-TXB2 contents, but a lower plasma nitrite plus nitrate level than the control group; 2) at rest, the SCI group had a higher platelet aggregability and [Ca(2+)]i, and O(X)-LDL-potentiated platelet activation than the control group; 3) O(X)-LDL-potentiated platelet aggregation was enhanced by strenuous arm exercise in both groups, but the effect of exercise was more pronounced in the SCI group than in the control group; 4) treating the platelet with L-arginine inhibited O(X)-LDL-potentiated platelet activation in both groups. The study concludes that individuals with SCI had more extensive resting and exercise-enhanced O(X)-LDL-potentiated platelet activation and greater amounts of preformed lipid peroxides than those without SCI. Therefore, supplementation therapy with antioxidants may be needed for patients with SCI, especially in a strenuous arm exercise period.

Topics: Adult; Arm; Arteriosclerosis; Calcium; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Dinoprost; Exercise Test; F2-Isoprostanes; Female; Humans; Lipid Peroxidation; Lipoproteins, LDL; Male; Nitrates; Nitric Oxide; Nitrites; Oxidative Stress; Platelet Activation; Platelet Aggregation; Platelet Count; Risk Factors; Spinal Cord Injuries; Thromboxane B2

Thromboxane A2 biosynthesis was studied in healthy subjects, in patients in whom the extent of carotid atherosclerosis was determined, and in patients receiving chronic aspirin treatment, to determine what factors activate platelets to develop carotid atherosclerosis. Urinary 11-dehydrothromboxane B2, a major metabolite of thromboxane A2, was measured by radioimmunoassay after purification by reverse-phase HPLC. The extent of carotid atherosclerosis was determined by real-time B-mode ultrasonography. The severity of carotid atherosclerosis in each subject was evaluated by plaque score, which was computed by summing the maximum thickness of plaque measured in millimeters. Urinary excretion of 11-dehydrothromboxane B2 in healthy subjects was higher (P < 0.01) in cigarette smokers (1063 +/- 244 ng/g creatinine) than in non-smokers (815 +/- 183 ng/g creatinine). Aspirin significantly suppressed 11-dehydrothromboxane B2 excretion (266 +/- 114 ng/g creatinine). In the 24 patients in whom the plaque score was measured, multivariate analysis indicated a significant positive correlation between urinary excretion of 11-dehydrothromboxane B2 and plaque score, age, smoking and hypercholesteremia. Our results indicate that risk factors such as age, hypercholesteremia, atherosclerosis and smoking activate platelets in vivo to develop carotid atherosclerosis.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Arteriosclerosis; Aspirin; Carotid Artery Diseases; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Multivariate Analysis; Platelet Activation; Risk Factors; Smoking; Thromboxane B2

Thromboxane A2 (TXA2) biosynthesis was studied in healthy subjects, patients with chronic cerebral infarction, patients under chronic aspirin treatment and patients with atrial fibrillation. Urinary 11-dehydro-TXB2, as a major metabolite of TXA2, was measured by radioimmunoassay. The extent of carotid atherosclerosis was determined by B-mode ultrasonography. The mean +/- SD urinary excretion in patients with cerebral infarction and distinct carotid-atherosclerotic lesions (1,725 +/- 239 ng/g creatinine, n = 6) was significantly higher (p less than 0.01) than in healthy subjects (911 +/- 239 ng/g creatinine, n = 44) and patients with cerebral infarction who had no distinct carotid lesion (1,050 +/- 191 ng/g creatinine, n = 6). The urinary excretion of healthy subjects was higher (p less than 0.01) in smokers (1,063 +/- 244 ng/g creatinine, n = 17) than in non-smokers (815 +/- 183 ng/g creatinine, n = 27). Aspirin largely suppressed 11-dehydro-TXB2 excretion (266 +/- 114 ng/g creatinine, n = 7). Three of 5 patients with atrial fibrillation showed very high values. Our results indicated that platelet activation occurs in the atherosclerotic lesions, and that urinary 11-dehydro-TXB2 is the appropriate analytic target for detecting platelet activation.

Topics: Adult; Aged; Arteriosclerosis; Aspirin; Atrial Fibrillation; Carotid Artery Diseases; Cerebral Infarction; Female; Humans; Male; Middle Aged; Platelet Activation; Thromboxane A2; Thromboxane B2

11-Dehydro-TxB2 and 2,3-dinor-TxB2 are products of the two major pathways of thromboxane metabolism in man. In this study we compared urinary excretion of 2,3-dinor-TxB2 and 11-dehydro-TxB2 as indices of Tx biosynthesis in vivo. We performed three studies to assess i) the relative abundance of these two metabolites in the urine of healthy subjects, ii) their cellular origin under physiological conditions and iii) their relative formation during platelet activation. In healthy normal volunteers urinary 11-dehydro-TxB2 is more abundant than 2,3-dinor-TxB2 (792 +/- 119 pg/mg creatinine vs 106 +/- 21 pg/mg creatinine). Administration of a dose of aspirin selective for platelet cyclooxygenase (20 mg/day for 10 days) caused substantial and comparable suppression of both 11-dehydro-TxB2 (mean 82 +/- 4.9%) and 2,3-dinor-TxB2 (mean 79 +/- 6.9%). recovery of excretion of both metabolites after a nonselective aspirin regimen (325 mg BID for 3 days) corresponded to platelet life-span. Furthermore, excretion of both metabolites was increased in patients with severe atherosclerosis consistent with the known increase in platelet activation in this setting. Quantitative analysis of both urinary 11-dehydro-TxB2 and 2,3-dinor-TxB2 by GC-MS established that, in contrast to previous assumptions, 11-dehydro-TxB2 is the most abundant urinary metabolite of TxB2. The aspirin study demonstrates that platelets are the major source of both metabolites in urine, consistent with their increased excretion in severe atherosclerosis. Combined analysis of both metabolites will distinguish altered metabolism from increased biosynthesis of thromboxane A2.

Topics: Adult; Arteriosclerosis; Blood Platelets; Female; Humans; Male; Reference Values; Thromboxane B2