thromboxane-b2 and Hyperlipidemias

There is an abundance of information suggesting that prostaglandins are involved in the development and clinical expression of atherosclerosis. Many studies demonstrate a relationship between prostaglandins and the risk factors for peripheral and coronary artery disease. Thus, part of the mechanism by which hyperlipidemia, diabetes mellitus, smoking, hypertension, sex hormones, age, heredity, emotional stress and diet contribute to the development and progression of atherosclerosis may be through an imbalance between thromboxane A2 and prostaglandin I2. Recent studies show a temporal relationship between acute ischemic events (specifically, unstable angina) and a transcardiac increase in thromboxane B2, while others demonstrate a salutary effect of disaggregatory and vasodilatory prostaglandins in such patients. If prostaglandins and thromboxane prove important in ischemic vascular disease, attention will be directed at the correction of their pathologic imbalance. This may be accomplished by dietary manipulation as well as by the development of prostaglandin receptor antagonists or inhibitors of specific prostaglandin pathways.

Topics: Age Factors; Arteriosclerosis; Coronary Disease; Diabetes Mellitus; Diet; Epoprostenol; Gonadal Steroid Hormones; Humans; Hyperlipidemias; Hypertension; Prostaglandin Antagonists; Prostaglandins; Receptors, Prostaglandin; Risk; Smoking; Stress, Physiological; Thromboxane A2; Thromboxane B2

High postprandial serum lipid concentrations are associated with increased oxidative stress which, in turn, increases the risk of atherosclerosis. Epidemiological studies correlate lower incidence of cardiovascular disease with adherence to the Mediterranean diet. The aim of this study was to evaluate changes in inflammatory (TXB(2) and LTB(4)) and oxidative stress markers (urinary hydrogen peroxide levels and serum antioxidant capacity), in addition to classic lipid parameters, after a fat-rich meal administered to 12 normolipemic, healthy subjects. Following a Latin square design, subjects were divided into three groups, each one receiving a different kind of oil (extra virgin olive oil; EVOO, olive oil; OO or corn oil; CO, together with 150g of potatoes), with 2-week washout periods between treatments. Blood samples were drawn at baseline and after 1, 2, and 6h after the meal. A significant decrease in inflammatory markers, namely TXB(2) and LTB(4), after 2 and 6h after EVOO (but not OO or CO) consumption and a concomitant increase of serum antioxidant capacity were recorded. These data reinforce the notion that the Mediterranean diet reduces the incidence of coronary heart disease partially due to the protective role of its phenolic components, including those of extra virgin olive oil.

Topics: Adult; Antioxidants; Blood Glucose; Cardiotonic Agents; Cholesterol, HDL; Cholesterol, LDL; Corn Oil; Coronary Disease; Diet, Mediterranean; Dietary Fats, Unsaturated; Flavonoids; Humans; Hyperlipidemias; Inflammation; Leukotriene B4; Male; Olive Oil; Oxidative Stress; Phenols; Plant Oils; Polyphenols; Postprandial Period; Thromboxane B2; Triglycerides

In vitro, olive phenols exert potent antioxidant and enzyme-modulating activities.. We comparatively evaluate, in mildly dyslipidemic patients, the vasoprotective potential of extra virgin olive oil.. 22 patients were administered 40 mL/day of either extra-virgin, i. e. phenol rich, or refined, i. e. phenol poor, olive oils (EVOO or ROO, respectively, with nearly identical fatty acid composition), with a crossover design. Each treatment was carried out for seven weeks, with four weeks of washout in between. Plasma antioxidant capacity, serum thromboxane B2 (TXB2) formation, and urinary isoprostane excretion were evaluated as surrogate markers of cardioprotective potential and vascular function.. No effects on plasma lipid/lipoprotein profile were observed. Conversely, EVOO consumption was associated with favorable effects on circulating markers. Namely, decreased serum TXB2 production and increased plasma antioxidant capacity were observed when EVOO was administered in both treatment arms. Neither treatment had any significant effect on isoprostane excretion.. EVOO consumption by mildly dyslipidemic patients is associated with favorable changes in circulating markers of cardiovascular condition. Based on current knowledge, these effects may be associated with cardioprotection.

Topics: Adolescent; Adult; Aged; Cardiovascular Diseases; Cross-Over Studies; Dietary Fats, Unsaturated; Female; Humans; Hyperlipidemias; Isoprostanes; Lipid Peroxidation; Lipids; Male; Middle Aged; Olive Oil; Oxidation-Reduction; Phenols; Plant Oils; Risk Factors; Thromboxane B2

To observe the clinical effect of Tongmai Jiangzhi Oral Liquid (TJOL) on blood lipid, lipid peroxidation, prostaglandin metabolism in treating coronary heart disease and angina pectoris with hyperlipidemia.. Forty-one cases in treated group and 24 in control group were treated with TJOL and Capsulae Oenoth Erae Biennisolei (COEB) for one month respectively. Serum lipid, apolipoprotein, plasma malonyldialdehyde (MDA), superoxide dismutase (SOD), thromboxane B2(TXB2), 6-keto-prostaglandin F1 alpha and blood glutathione peroxidase (GSH-Px) were measured before and after treatment.. After treatment with TJOL, the total effective rate was 87.80% in relieving angina and 50.00% in improving ECG. Other data showed that the levels of serum TC, TG, apoB, plasma MDA, TXB2 and TXB2/6-keto-prostaglandin F1 alpha ratio lowered and levels of apoA, GSH-Px, serum HDL-C, apoA1/apoB increased (P < 0.05-P < 0.001).. TJOL could effectively lower blood lipid, reduce injury caused by free radicals, regulate prostaglandin metabolism and treat coronary heart disease. By this study, an effective prescription of Chinese herbal medicine was offered for prevention and treatment of coronary heart disease.

Topics: Adult; Aged; Apolipoproteins; Coronary Artery Disease; Female; Humans; Hyperlipidemias; Lipid Peroxidation; Male; Middle Aged; Superoxide Dismutase; Thromboxane B2

Astaxanthin (ASTX) is a xanthophyll carotenoid that reduces hemostasis in hyperlipidemic organisms. Its antihemostatic mechanisms remain unclear.. The effects of ASTX on coagulation, the fibrinolytic system and platelet aggregation were investigated in hyperlipidemic rats.. Different doses of ASTX (5, 10 and 30 mg/kg/day, p.o.) were administered for four weeks to high-fat diet-induced hyperlipidemic rats. Serum lipid and lipoprotein levels were measured with an automatic biochemical analyzer. The prothrombin time (PT), activated partial thromboplastin time (APTT) and maximum platelet aggregation rate (MAR) were determined by a coagulation analyzer. The activities of the tissue-type plasminogen activator (t-PA), type-1 plasminogen activator inhibitor (PAI-1) and endothelial nitric oxide synthase (eNOS), as well as the levels of thromboxane B(2) [TXB(2)], 6-keto prostaglandin F(1α) [6-keto-PGF(1α)] and platelet granule membrane protein (GMP-140), were measured with enzyme-linked immunosorbent assay kits. Gene and protein expression levels were analyzed by reverse transcriptase polymerase chain reaction and Western blot, respectively.. ASTX (30 mg/kg) treatment in hyperlipidemic rats reduced serum TG (0.58 ± 0.14 versus 1.12 ± 0.24 mmol/L), serum TC (1.77 ± 0.22 versus 2.24 ± 0.21 mmol/L), serum LDL-C (1.13 ± 0.32 versus 2.04 ± 0.48 mmol/L), serum MDA (69%), plasma MAR (55%), serum TXB2/6-keto-PGF1α (34%) and serum GMP-140 levels (25%), plasma PAI-1 activity (48%) and downregulated the mRNA (33%) and protein (23%) expression of aorta eNOS, the mRNA (79%) and protein (72%) expression levels of aorta PAI-1. However, ASTX (30 mg/kg/d) treatment increased serum SOD activity (2.1 fold), serum GPx activity (1.8 fold), plasma PT (1.3 fold), plasma APTT (1.7 fold), serum NO (1.4-fold), serum 6-keto-PGF1α (1.3 fold).. ASTX reduced blood coagulation and platelet aggregation and promoted fibrinolytic activity in hyperlipidemic rats. These activities were closely correlated with ASTX, maintaining the balance of t-PA/PAI-1, NO/ROS and TXA2/PGI2 in vivo.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anticoagulants; Biomarkers; Blood Coagulation; Diet, High-Fat; Disease Models, Animal; Dose-Response Relationship, Drug; Fibrinolysis; Fibrinolytic Agents; Hyperlipidemias; Lipid Peroxidation; Lipids; Male; Nitric Oxide; Nitric Oxide Synthase Type III; P-Selectin; Partial Thromboplastin Time; Plasminogen Activator Inhibitor 1; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prothrombin Time; Rats, Sprague-Dawley; Thromboxane B2; Time Factors; Tissue Plasminogen Activator; Xanthophylls

Previous studies have demonstrated that statin can reduce the risk of acute coronary syndrome. In order to explore the mechanism, we observed the effects of pravastatin on plaque stability in atherosclerotic rabbits. Sixteen male rabbits were fed with a high fat diet following their damaged abdominal aortic endothelium by using catheter. Eight of them were administered with pravastatin (10 mg·kg(-1)·d(-1)) for 4 weeks. Then the rabbit atherosclerotic plaque rupture and thrombosis were triggered by injection of viper venom and histamine. Compared with model group, the thrombus area on aorta in pravastatin-treated group was reduced. Fibre cap on plaque was more thick and integrant, and inflammatory cell infiltration was also decreased. Serum total cholesterol, triglyceride, low density lipoprotein-cholesterol and contents of cholesterol in abdominal aorta were decreased. 6-Keto-prostaglandin F(1α) (6-keto-PGF(1α)) level and ratio of 6-keto-PGF(1α)/thromboxane B(2) (TXB(2)) in aorta were significantly increased. These results suggested that pravastatin could increase plaque stability and inhibit thrombosis through both lipid-dependent and lipid-independent way.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anticholesteremic Agents; Aorta; Aorta, Abdominal; Atherosclerosis; Cholesterol; Cholesterol, LDL; Diet, High-Fat; Disease Models, Animal; Histamine; Hyperlipidemias; Male; Plaque, Atherosclerotic; Pravastatin; Rabbits; Thrombosis; Thromboxane B2; Triglycerides; Viper Venoms

To investigate the relations of platelet phospholipid fatty acids to thrombotic risk factors in the middle-aged and geriatric patients with hyperlipidemia in the metropolitan area of Hangzhou, Zhejiang province.. A questionnaire survey was conducted among 81 patients with hyperlipidemia, 50 males and 31 females, aged (57 +/- 8), and 65 healthy controls, 43 males and 22 females, aged (58 +/- 9) to collect the data about height, weight, and diet. Peripheral venous blood samples were collected to examine the total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), homocysteine (Hcy), 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)), and thromboxane B(2) (TXB(2)) were examined by standard methods. Serum thrombotic risk factors including homocysteine and Thromboxane B(2) were determined by standard methods. Platelet phospholipid fatty acids were examined by gas chromatography. The correlation between the serum thrombotic risk factors (Hcy, TXB(2), and 6-keto-PG F1a) was analyzed by multivariate linear regression.. There were no significant differences in platelet phospholipid fatty acids between the patients with hyperlipidemia and the healthy controls. Serum Hcy was significantly negatively correlated with docosahexaenoic acid (DHA) and the ratio of n-3 PUFA (polyunsaturated fatty acids)/n-6 PUFA (r = -0.277 and -0.231, both P < 0.01). The level of serum TXB(2) was significantly positively correlated with arachidonic acid (r = 0.176, P < 0.05), and significantly negatively correlated with DHA (r = -0.209, P < 0.01), eicosapentaenoic acid (EPA) (r = -0.194, P < 0.05), and n-3 PUFA/n-6 PUFA (r = -0.238, P < 0.01).. Increasing the ratio of n-3 PUFA/n-6 PUFA in platelet phospholipid may potentially decrease the thrombotic risks such as Hcy and TXB(2) and provide a reference for diet selection.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Arachidonic Acid; Blood Platelets; Cholesterol; Dietary Fats; Fatty Acids; Female; Homocysteine; Humans; Hyperlipidemias; Linear Models; Male; Middle Aged; Multivariate Analysis; Phospholipids; Risk Factors; Surveys and Questionnaires; Thrombosis; Thromboxane B2

The study was designed to assess blood platelet sensitivity to acetylsalicylic acid and its associations with dyslipidaemia and inflammation in coronary artery disease patients. Platelet non-responsiveness to aspirin is associated with an increased risk of serious cardiovascular events. Several environmental and hereditary factors are reportedly involved in sub-optimal acetylsalicylic acid response. Forty-five coronary artery disease patients and 45 non-coronary artery disease controls received acetylsalicylic acid at a daily dose of 75-150 mg. Controls were examined twice: on the day of entering the study and 10 days later. Urinary 11-dehydrothromboxane B2 was assessed as the marker of platelet thromboxane generation. Aggregation was studied in platelet-rich plasma using turbidimetric aggregometry with collagen and arachidonic acid. Fifty to seventy percent of coronary artery disease patients showed an extent of collagen-induced aggregation above the upper quartile of the reference range compared with 8-15% in controls (P<0.003). For arachidonic acid-activated aggregation these proportions were 45-50% in coronary artery disease versus 7% in controls (P<0.007). In coronary artery disease patients, the acetylsalicylic acid-mediated platelet inhibition positively correlated with increased triglycerides (in arachidonic acid-stimulated platelets, r=0.30, P=0.0018), total cholesterol (r=0.33, P<0.0001 in coll and arachidonic acid-activated platelets) and elevated serum C-reactive protein (CRP) (r=0.27, P=0.0024). In coronary artery disease patients urine 11-dehydrothromboxane B2 concentrations were significantly increased compared to controls after 10 day acetylsalicylic acid intake (563; 313-728 pg/mg creatinine versus 321; 246-488 pg/mg creatinine, P=0.04). The incidence of suboptimal acetylsalicylic acid response incidence was more common in patients with coronary artery disease. Acetylsalicylic acid inhibition of blood platelet reactivity and thromboxane generation was less effective in these patients. Dyslipidaemia and chronic inflammatory states may promote suboptimal acetylsalicylic acid response in coronary artery disease patients.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Blood Platelets; C-Reactive Protein; Cholesterol; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Inflammation; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Thromboxane B2; Triglycerides

Hyperlipemia rabbit models established with high cholesterol and fat diet were treated with direct moxibustion and medicinal cake-separated moxibustion. The post-treatment plasma 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) and thromboxane B2 (TXB2) contents were determined by radioimmunoassay. Results indicated that the plasma 6-keto-PGF1alpha content significantly increased, the TXB2 level decreased (P < 0.05) and the TXB2 /6-keto-PGF1alpha ratio also decreased (P < 0.01) in the medicinal cake-separated moxibustion group as compared with those in the model group respectively, but there was no significant difference between the medicinal cake-separated moxibustion group and the direct moxibustion group (P > 0.05), suggesting that both the medicinal cake-separated moxibustion and direct moxibustion can regulate the plasma 6-keto-PGF1alpha and TXB2 contents, and the TXB2/6-keto-PGF1alpha ratio with similar actions, and have a certain protective action on endothelial cells of the aorta in the rabbit of hyperlipemia.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Female; Hyperlipidemias; Male; Moxibustion; Rabbits; Radioimmunoassay; Thromboxane B2

The roles of platelet function, plasma lipids and nitric oxide (NO) were studied in adolescent patients with essential hypertension (JEHT group), with chronic renal failure (CRF) associated with hypertension (CRFH group), and CRF patients with normal blood pressure (CRF group), as compared with normal controls (cont. group). Platelet aggregation and the thromboxane B(2)(TxB(2)) level were significantly higher in the JEHT and CRFH groups as compared with the cont. group, whereas they were significantly lower in the CRF group. On the other hand, the platelet cAMP level was significantly lower in the JEHT and CRFH groups than in the cont. group. The plasma NO level was significantly higher only in the JEHT as compared with the cont. group (120 +/- 39 and 89 +/- 21 microM, respectively). The plasma total cholesterol, triglyceride and LDL cholesterol concentrations were normal in the JEHT group, but high in the CRF and CRFH group, the HDL cholesterol level was lower in the CRF and CRFH groups as compared with the cont. and JEHT groups. There was a positive correlation between the platelet aggregation and the TxB(2)level and between the BP and the platelet aggregation. In conclusion, hyperlipidaemia is commonly present in uraemia with haemodialysis, but is not specific for hypertension in children, while an increased platelet function is frequently associated with hypertension. The increased NO level might play a compensatory role in JEHT.

Topics: Adolescent; Blood Pressure; Child; Cyclic AMP; Dialysis; Female; Humans; Hyperlipidemias; Hypertension; Lipids; Lipoproteins; Male; Nitric Oxide; Platelet Aggregation; Renal Insufficiency; Thromboxane B2

Olive oil is the main source of dietary fatty acids in the Mediterranean region. The objective of this study was to evaluate the effect of dietary supplementation with virgin olive oil in an experimental model with rabbits fed an atherogenic diet (saturated fat 48% of total fat). Four different groups of 10 animals each were studied: (1) normolipemic diet (NLD), (2) atherogenic diet or saturated fatty acid-enriched diet (SFAED), (3) NLD with 15% olive oil (NLD+OLIV), and (4) SFAED with 15% virgin olive oil (SFAED+OLIV). The animals were fed the experimental diets for 6 weeks, after which we determined serum lipid profile (total cholesterol, HDL-cholesterol, and triglycerides), platelet aggregation, platelet thromboxane B(2), aortic prostacyclin, and platelet and vascular lipid peroxidation. Scanning electron microscopic images of the vascular endothelium were studied, as were morphometric parameters in the arterial wall and thrombogenicity of the subendothelium (annular perfusion chamber). Animals fed the SFAED showed platelet hyperactivity and increased subendothelial thrombogenicity. Animals fed the SFAED+OLIV showed, compared with the SFAED group, an improved lipid profile with decreased platelet hyperactivity and subendothelial thrombogenicity and less severe morphological lesions of the endothelium and vascular wall. We conclude that supplementation of the SFAED with 15% olive oil reduced vascular thrombogenicity and platelet activation in rabbits. Although the percentage of olive oil in the diet was higher than the amount in the human diet, these results may be helpful in determining the effect of olive oil in the human thrombogenic system.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta; Arteriosclerosis; Cholesterol; Diet, Atherogenic; Disease Models, Animal; Drug Evaluation, Preclinical; Endothelium, Vascular; Fatty Acids; Fatty Acids, Unsaturated; Fibrinolytic Agents; Hyperlipidemias; Lipids; Male; Malondialdehyde; Microscopy, Electron, Scanning; Olive Oil; Plant Oils; Platelet Aggregation; Rabbits; Stress, Mechanical; Thrombosis; Thromboxane B2

This investigation sought to determine how different components of the hemostatic system affect the development of venous thrombosis in rats displaying hyperlipidemia, either on a genetic basis or secondary to metabolic disorders. On employing an experimental model of collagen-triggered venous thrombosis, both spontaneously hyperlipidemic (Yoshida strain) and streptozotocin-induced diabetic rats generated about 2.3-fold greater thrombi than normolipidemic controls. This was associated with significant platelet activation, as revealed by increased levels of serum thromboxane B2 in diabetics (1.5-fold) as well as in Yoshida (8-fold) rats, in comparison with controls. In contrast, ex vivo total fibrinolytic activity, as measured by euglobulin lysis time, did not differ between normo- and hyperlipidemic or diabetic animals. Plasminogen activator inhibitor activity was lower in both Yoshida and diabetic rats than in controls. However, tissue-type plasminogen activator activity was differently affected by the genetic or the diabetes-related hyperlipidemia, showing significantly lower values in Yoshida (-26%), but significantly higher values in diabetic rats (+29%) than in normolipidemic controls. We conclude that platelet activation, rather than consistent modifications of the fibrinolytic system, is likely to influence the enhanced thrombus development associated with primary or secondary forms of hyperlipidemia.

Topics: Animals; Disease Models, Animal; Fibrinolysis; Hyperlipidemias; Male; Platelet Activation; Rats; Rats, Inbred BN; Rats, Inbred Strains; Rats, Sprague-Dawley; Thrombophlebitis; Thromboxane B2

The effects of a soybean oil diet and a high-cholesterol oil (HC) diet, and an HC diet with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) supplementation, on basal and postpreservative cardiac function of the hearts and on postpreservative renal function of the kidneys from older rats were examined.. Groups 1 through 4 of 100-week-old rats were fed either soybean oil, HC, HC with EPA, or HC with DHA, respectively, for 12 weeks. Blood was collected for analysis of plasma fatty acids, and the heart and left kidney were removed from the rat. In experiment 1, the heart was perfused on a Langendorff apparatus. After evaluation of the cardiac function of each rat, the heart was stored in histidine-tryptophan-ketoglutarate solution for 8 hr at 4 degrees C. The heart was reperfused and the recovery of cardiac function was evaluated. The coronary perfusate during reperfusion was collected to measure 6-keto prostaglandin F1alpha and thromboxane B2. Coronary flow (CF) perfused with Krebs-Henseleit bicarbonate (KHB) solution containing 5-hydroxytryptamine (5-HT) and nitroglycerin were evaluated in the Langendorff mode with atrial pacing (330 beats/min). In experiment 2, the excised left kidney was immediately flushed and preserved with University of Wisconsin solution for 8 hr at 4 degrees C. The kidney was then reperfused with KHB solution and renal function was evaluated.. The plasma and cardiac EPA levels in group 3 were significantly higher than the levels found in the other groups. The plasma and cardiac ratios of EPA to arachidonic acid were significantly higher in groups 3 and 4 than in groups 1 and 2. There were no significant differences in basal cardiac function among any of the diet-fed rats. The percentage values of the recovery of aortic flow, cardiac output (CO), and left ventricular max dp/dt in group 3 and CO in group 4 were significantly higher than in group 2. In addition, the recovery of CF in group 3 tended to be higher than in group 2 (P=0.07). The percentage values of the recovery of aortic flow, CF, CO, and left ventricular max dp/dt in group 1 were significantly lower than in the other dietary groups. CF reperfused with KHB solution containing 5-HT was significantly higher in group 3 than in groups 1 and 2. CF reperfused with KHB solution containing 5-HT was significantly higher in group 4 than in group 1. CF reperfused with KHB solution containing nitroglycerin in group 3 tended to be higher than in groups 1 and 2 (P=0.07). The thromboxame B2 concentrations in the coronary perfusate during reperfusion in groups 3 and 4 were significantly lower than in groups 1 and 2. Fractional sodium reabsorption in group 3 was significantly higher than in group 2. Inulin clearance in groups 3 and 4 was significantly higher than in group 1. The postpreservative urinary flow in group 3 was significantly higher than in groups 1 and 2. The urinary flow was significantly higher in group 4 than in group 1.. These results suggest that EPA administration may attenuate preservation and reperfusion injury and improve the recovery of cardiac and renal functions in hyperlipidemic and older rats. DHA administration may also show beneficial effects on kidney preservation in hyperlipidemic rats.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Weight; Cholesterol, Dietary; Dietary Fats, Unsaturated; Eating; Fatty Acids, Omega-3; Female; Glucose; Heart; Hyperlipidemias; Kidney; Lipids; Nitroglycerin; Organ Preservation; Rats; Rats, Wistar; Reperfusion; Serotonin; Thromboxane B2; Tromethamine

The authors observed the changes pf symptoms and signs, obesity index, lipid index (TC, TG, LDL-C, HDL-C), atherosclerosis in dex (AL), ratio of waist centimetre to hip centimetre (W. C/H. C). TXB2 and 6-Keto-PGF1 alpha in 34 simple obesity patients complicated with hyperlipidemia before and after acupuncture so as to make clear the influence of acupuncture on pathogenic factors led up to circular diseases. The results showed that the marked weight loss effect was achieved in the cases by acupuncture, while the level of TC, TG, LDL-C, HDL-C, AI, W.C./H.C, TXB2, 6-Keto-PGF1 alpha in the patients were finely regulated. It suggests that the acupuncture treatment not only treated obesity and hyperlipidemia, but also resisted the pathogenic factors led up to circular diseases.

Topics: 6-Ketoprostaglandin F1 alpha; Acupuncture Therapy; Adult; Aged; Female; Humans; Hyperlipidemias; Infant; Male; Middle Aged; Obesity; Thromboxane B2

The study was performed to investigate the influence of lipoproteins (LP) on the thromboxane (TX) A2 formation capacity of platelets in clotting whole blood in vitro. The different lipoprotein fractions VLDL, LDL, HDL2 and HDL3 were isolated from blood of normo- or dyslipidemic volunteers by ultracentrifugation. These lipoproteins were incubated in blood with different levels of serum total cholesterol (TC) taken from normolipidemics (TC < 200 mg/dl), moderate hypercholesterolemics (TC: 200-250 mg/dl) or subjects with high cholesterol level (TC > 250 mg/dl), respectively. The amount of serum TXA2 formed within 60 min at 37 degrees C was measured by enzyme immunoassay. The results obtained show that the efficacy of separate LP fractions to influence the TXA2 production depends not only on the type of LP fraction but also on the source of plasma used for isolation of LP and on the cholesterol level in the blood for incubation: LDL taken from normolipidemics or moderate hyperlipidemics inhibited the TXA2 formation in blood from normolipidemics (P < 0.02, respectively), but enhanced it in blood from persons with moderate hypercholesterolemia (P < 0.05). LDL from hyperlipidemics enhanced TXA2 production in blood from hyperlipidemics (P < 0.05). The HDL2 fractions inhibited the TXA2 formation in blood from normo- and hypercholesterolemics (P < 0.02, resp.), but there was no effect of HDL2 in clotting blood from persons with moderate hypercholesterolemia. All HDL3 fractions tested inhibited the TXA2 formation in all types of blood used for clotting (P < 0.02, resp.), probably due to their great cholesterol accepting capacity.

Topics: Blood Coagulation; Blood Platelets; Humans; Hypercholesterolemia; Hyperlipidemias; In Vitro Techniques; Lipoproteins; Thromboxane A2; Thromboxane B2

The influence of HDL, isolated from normolipidemic human blood and blood of normo- and hyperlipidemic rabbits, on in vitro 6-keto-PGF1 alpha synthesis by rabbit aorta and on TXB2 synthesis by platelets of clotting human and rabbit blood was tested. The HDL fraction from normolipidemic subjects, when incubated with blood from normolipidemic humans or rabbits, inhibited TXB2 formation. The same fraction stimulated the formation of 6-keto-PGF1 alpha after incubation with rabbit aorta taken from normolipidemic animals. HDL taken from hyperlipidemic rabbits inhibited 6-keto-PGF1 alpha formation in rabbits and had no influence on TXB2 formation. These results support the hypothesis that not only is the absolute amount of HDL important for its influence on prostanoid formation, but also the origin and the composition of the HDL fraction.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta; Blood Coagulation; Blood Platelets; Humans; Hyperlipidemias; In Vitro Techniques; Lipoproteins, HDL; Rabbits; Species Specificity; Thromboxane B2

Platelet function after thrombin stimulation, the fatty acid composition of individual phospholipids, and levels of lipid components (cholesterol, cholesterol ester, phospholipids and triglycerides) were determined in total membranes of platelets from hyperlipidaemic (HL) and control subjects. Platelet aggregation, thromboxane (TX) B2 production and serotonin release was significantly greater in HL patients than in controls. Levels of platelet cholesterol, total phospholipids, cholesterol ester and triglycerides, were significantly higher in the HL patients. Small differences between the two groups were observed for the phospholipid fatty acid patterns. However, levels of arachidonic acid (AA) were significantly higher in phosphatidylinositol (PI) of HL patients (40.01 +/- 6.59 mol%) as compared to the controls (31.52 +/- 9.91 mol%) (P = 0.002). The higher levels of AA in PI, which is considered a donor pool for eicosanoid synthesis, may be an additional mechanism for the well documented platelet hyperfunction and greater TXB2 production in hyperlipidaemic subjects.

Topics: Adult; Blood Platelets; Cell Membrane; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Fatty Acids; Humans; Hyperlipidemias; Male; Middle Aged; Phospholipids; Platelet Aggregation; Serotonin; Thromboxane B2; Triglycerides

The purpose of this study was to verify the effect of a Chinese herbal medicine Jiang-Zhi Zhong-Yao-Pian to reduce serum lipoid. Efficacy was observed in 30 cases of hyperlipemia; 20 cases administered with evening primose oil capsules were taken as controls. Each group took drugs for two or three months. The results were as follows: After treatment as compared with before treatment, the serum levels of TC, TG and TXB2 dropped from 264.28 +/- 70.52 mg%, 393.52 +/- 250.42 mg% and 110.75 +/- 43.52 pg/ml to 225.60 +/- 50.93 mg%, 264.97 +/- 252.81 mg% and 88.82 +/- 46.50 pg/ml respectively (P less than 0.001, less than 0.01, less than 0.05). However, in the group taking evening primrose oil capsules, TC, TG and TXB2 in comparing with the pre-treatment levels were changed from 251.33 +/- 58.24 mg%, 316.35 +/- 104.93 mg% and 131.53 +/- 49.77 pg/ml to 244.30 +/- 43.28 mg%, 272.10 +/- 92.52 mg% and 115.33 +/- 47.49 pg/ml respectively (P greater than 0.05, less than 0.05, greater than 0.05). This medicine had no side-effect. The results showed that the herbal formula might be useful to reduce serum TC, TG and TXB2.

Topics: 6-Ketoprostaglandin F1 alpha; Cholesterol; Drugs, Chinese Herbal; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; Male; Middle Aged; Tablets; Thromboxane B2; Triglycerides

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Hyperlipidemias; Lipid Peroxidation; Lipid Peroxides; Male; Pollen; Rabbits; Thromboxane B2; Zea mays

The authors examined the influences of nifedipine and Paeonia lactiflora (PL) on plasma LPO, TXB2 and 6-keto-PGF1 alpha in cholesterol-fed rabbits. In this study, oral administration of nifedipine (15 mg/kg per day) and PL (0.5 g/kg per day) with 2% cholesterol diet for 15 weeks caused 60.75% and 74.24% reduction in the lesion area of aorta respectively. The levels of plasma LPO, TXB2, cholesterol, phospholipid and calcium of the intimalmedia of the aorta in the treated groups were significantly lower than those in the control group, but the level of 6-keto-PGF1 alpha in the treated groups was significantly higher. The durations of TXB2 elevation and 6-keto-PGF1 alpha reduction were delayed. The ratio of TXB2/6-keto-PGF1 alpha tended to balance. The ratio of TXB2/6-keto-PGF1 alpha was significantly positive correlation with the percentage of lesion area of the aorta. It is demonstrated that calcium metabolism plays an important role in thromboxane, prostaglandin, and LPO synthesis. In conclusion, the inhibition of LPO production and the regulation of TXA2-PGI2 balance may be one of the mechanisms of anti-atherogenesis of calcium antagonists and PL.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Cholesterol, Dietary; Drugs, Chinese Herbal; Hyperlipidemias; Male; Nifedipine; Rabbits; Thromboxane B2

New Zealand strain white male rabbits were divided into four groups to study the effects of 8501, extracted from a Chinese herb, on hyperlipidemia and the TXA2/PGI2 ratio in atherosclerotic rabbits. The results indicate that serum cholesterol and the levels of cholesterol and cholesteryl ester in aortic tissue were significantly increased in cholesterol-fed rabbits. The percentage of alpha-lipoprotein was significantly decreased and the aortic atherosclerotic plaque area was significantly increased. The data also demonstrate that the level of plasma TXB2 was markedly increased, while that of 6-keto-PGF1 alpha was significantly decreased. The TXB2/6-keto-PGF1 alpha ratio (T/6) was significantly increased. The decrease of 6-keto-PGF1 alpha occurred prior to the increase of TXB2. Compound 8501 not only lowered serum total cholesterol and aortic total cholesterol and cholesteryl ester but also antagonized the decrease of alpha-lipoprotein and atherosclerotic plaque formation. In addition, 8501 prevented the decrease of plasma 6-keto-PGF1 alpha and the increase of TXB2, and so the T/6 ratio was significantly decreased.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Drugs, Chinese Herbal; Hyperlipidemias; Hypolipidemic Agents; Male; Rabbits; Thromboxane B2

The mechanisms responsible for hyperfiltration in diabetes mellitus (DM) as well as for the initiation and progression of diabetic nephropathy are not fully elucidated. Enhanced prostaglandin E2 (PGE2) production has been invoked in the former and thromboxane (TXB2) and hyperlipidemia in the latter. Fish oil (FO)-enriched diets can favorably alter eicosanoid synthesis and serum lipid profiles. We therefore examined the effects of a FO-enriched diet on glomerular filtration (GFR), proteinuria, glomerular eicosanoid production, and serum lipids in rats with streptozotocin-induced DM (STZ-DM). Groups of 5-8 rats with STZ-DM were maintained on low insulin and then pair-fed with isocaloric diets enriched with either FO (20% w/w) or beef tallow (BT; 20% w/w). GFR was determined in the same animals at onset of diet and after 8 and 20 weeks on the respective diets by [14C]inulin clearance using implanted osmotic minipumps each time. Significant hyperfiltration was present initially and GFR did not change on either diet for 20 weeks, in spite of a significant and greater than 50% decrease in all prostaglandins (PGE2, TXB2, PGF2 alpha, 6-keto, PGF1 alpha) produced by glomeruli isolated from DM/FO as compared to DM/BT or control rats. FO diet completely corrected the hypertriglyceridemia of diabetes and significantly reduced the mild and early proteinuria of DM. The decrease in proteinuria and the correction of hyperlipidemia of DM by a FO-enriched diet may be beneficial in the long term not only for the development of diabetic glomerulopathy, but also for the accelerated atherosclerosis of DM.

Topics: Animals; Diabetes Mellitus, Experimental; Dinoprostone; Eicosanoids; Female; Fish Oils; Glomerular Filtration Rate; Hyperlipidemias; Kidney; Kidney Glomerulus; Lipids; Lipoproteins; Organ Size; Proteinuria; Rats; Rats, Inbred Strains; Thromboxane B2

In young patients with borderline arterial hypertension and, to a greater extent, with Stage 1 hypertensive disease (HD), changes were found in the proatherogenic plasma lipid and apoprotein composition, which were manifested as higher levels of total cholesterol, triglycerides, low and very low density lipoprotein cholesterols along with increased apolipoprotein B and apolipoprotein B:apolipoprotein AI ratio. The prostacyclin-thromboxane system in borderline arterial hypertension was in an activated state by retaining the physiological ratio of its components. The patients with Stage I HD exhibited a considerable increase in thromboxane activity, which determined the system's imbalance towards its predominance. In Stage I HD, the thrombocytic link of hemostasis was characterized by enhanced platelet aggregability mediated by the imbalance of the prostacyclin-thromboxane system in the direction of thromboxane.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Arteriosclerosis; Epoprostenol; Female; Humans; Hyperlipidemias; Hypertension; Lipids; Male; Platelet Aggregation; Thromboxane A2; Thromboxane B2; Time Factors

Fifteen healthy volunteers were treated for 30 days with 5 g daily fish oil in capsule form (MaxEPA). After that time, serum triglycerides had decreased by a mean of 26% (p less than 0.05). This relative decrease in triglycerides was the larger the higher were the baseline levels before the start of therapy (p less than 0.01). Total cholesterol remained unchanged with fish oil. HDL-cholesterol showed a small mean increase by 12% (p less than 0.10). The rate of platelet aggregation after induction with collagen 1 microgram/ml was reduced after 30 days of therapy (p less than 0.05), while no effect on platelets was observed with collagen 5 micrograms/ml or ADP (0.5, 1 and 10 mumol/l) as aggregating agents. In vitro thromboxane synthesis after stimulation with collagen (1 microgram/ml) or arachidonic acid (1 mmol/l) was inhibited cumulatively by fish oil and, after 30 days, reached 56% (p less than 0.02) and 44% (p less than 0.05) of the initial values, respectively. Both the basal and prostaglandin E1 stimulated concentrations of c-AMP in platelet rich plasma remained uninfluenced. Thus, the ingestion of a low dose of fish oil by young and healthy subjects led to significant changes in serum triglycerides and platelet function.

Topics: Administration, Oral; Adult; Cholesterol, HDL; Eicosapentaenoic Acid; Female; Humans; Hyperlipidemias; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Thromboxane B2; Triglycerides

The objective of this work was to characterize changes in platelet aggregability during postprandial hypertriglyceridemia with special emphasis on arachidonic acid metabolism. Ten healthy young men consumed 100 g fat after a fasting period of 12 hr. In-vitro platelet aggregation induced by ADP and collagen was measured at 0, 3, 5, and 9 hours after the fat intake. The major arachidonic acid metabolites, 12-hydroxyeicosatetraenoic acid (12-HETE), thromboxane A2 (TXA2), prostaglandin F2 alpha (PGF2a), and prostaglandin E2 (PGE2) produced during collagen-induced platelet activation were quantified by gas chromatography/mass spectrometry. A significant decrease in platelet aggregability induced by both ADP and collagen was detected during the postprandial hyperlipemia. No significant changes could be found in the prostanoid pattern of collagen activated platelets. There was no correlation between the degree of the inhibition of platelet aggregation and the relative or absolute increase of triglyceride-levels in the plasma during the postprandial hyperlipemia.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Adult; Arachidonic Acids; Cholesterol; Dietary Fats; Gas Chromatography-Mass Spectrometry; Humans; Hydroxyeicosatetraenoic Acids; Hyperlipidemias; Male; Phospholipids; Platelet Aggregation; Prostaglandins; Thromboxane B2; Triglycerides

The effects of alimentary hypercholesterolemia and nephrotic hyperlipidemia, alone and in combination, on rat peritoneal macrophage phagocytosis, basal eicosanoid production, and glomerular macrophage number during peak PA nephrosis were evaluated in rats fed four different diets: 1) normal/standard chow; 2) PA/standard chow; 3) normal/cholesterol-supplemented diet; and 4) PA/cholesterol-supplemented diet. Both PA/standard chow and normal/cholesterol-supplemented rodent groups manifested significantly greater peritoneal macrophage phagocytosis and glomerular macrophage number when compared with normal/standard chow animals. However, the combination of the nephrotic state with superimposed alimentary hypercholesterolemia (PA/cholesterol-supplemented group) produced the greatest rise in these parameters, a rise that was significantly greater than was produced in the three other groups. Regarding basal eicosanoid production by macrophages, there was a numerical trend toward increased production of thromboxane B2 in the PA/standard chow animals and normal/cholesterol-supplemented rats when compared with normal/standard chow. Again, the combination of nephrosis and alimentary hypercholesterolemia in the PA/cholesterol-supplemented group was associated with a significantly greater amount of thromboxane B2 generated when compared with the other three groups. Regarding PGE2 production, there were no significant differences among the groups, despite marked differences in fasting serum lipid levels. This data suggest that there is a synergistic effect between alimentary hypercholesterolemia and the secondary hyperlipidemia of nephrosis in producing these macrophage functional alterations. Because fasting triglyceride values between the two nephrotic groups were indifferent, one can further speculate that it is the elevation of the serum cholesterol value that predominantly evokes these changes in macrophage function.

Topics: Animals; Cell Count; Cholesterol; Dinoprostone; Eicosanoids; Hypercholesterolemia; Hyperlipidemias; Kidney Glomerulus; Macrophages; Male; Nephrosis; Nucleosides; Peritoneal Cavity; Phagocytosis; Proteinuria; Rats; Rats, Inbred Strains; Thromboxane B2; Triglycerides

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Cholesterol; Female; Hyperlipidemias; Leeches; Male; Materia Medica; Rabbits; Thromboxane B2; Triglycerides

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta; Cholesterol; Cholesterol, HDL; Hyperlipidemias; Male; Medicine, Chinese Traditional; Plants, Medicinal; Pollen; Rabbits; Thromboxane B2

We studied the effect of cod-liver oil on the development and progression of coronary artery disease in swine subjected to coronary balloon abrasion and fed an atherogenic diet for eight months. Sections from serial 3-mm segments of the coronary arteries were analyzed morphometrically in 7 pigs given a cod-liver-oil supplement and 11 control animals not given the supplement. Significantly less disease was seen in the sections from the animals fed cod-liver oil. The mean lesion area per vessel, mean luminal encroachment per vessel, and mean maximal luminal encroachment per vessel were reduced in animals fed cod-liver oil, as compared with controls, (P = 0.05, P = 0.016, and P = 0.011, respectively). Both groups of animals had severe hyperlipidemia throughout the study. Differences in the extent of coronary atherosclerosis were not related to differences in plasma lipid levels. Platelet arachidonate was markedly reduced, platelet eicosapentaenoic acid was increased, and serum thromboxane was decreased in the oil-fed group as compared with the control group. We conclude that in our animal mode, dietary cod-liver oil retarded the development of coronary artery disease, possibly through changes in prostaglandin metabolism.

Topics: Animals; Arachidonic Acids; Blood Platelets; Cod Liver Oil; Coronary Disease; Coronary Vessels; Diet, Atherogenic; Disease Models, Animal; Fish Oils; Hyperlipidemias; Lipids; Male; Swine; Thromboxane B2

The mechanism of thrombus formation in hyperlipidemia was studied. Attempts at artificial creation of an arterial thrombus in control rabbits stenosing the femoral artery by ligature were not successful unless ellagic acid was administered by injection. However, in rabbits with hyperlipidemia, mere creation of stenosis in the femoral artery resulted in a high percentage of thrombus formation. In rabbits with hyperlipidemia, both thromboxane (Tx) A2 biosynthesis in platelets and prostacyclin (PGI2) biosynthesis in the aorta were increased and these changes were noted at the level of cyclooxygenase in the arachidonic acid metabolic pathway. Therefore, these results suggest that thrombi are likely to be formed in hyperlipidemia and that such thrombus formation is due largely to platelet hyperfunction.

Topics: Animals; Aorta, Thoracic; Arachidonic Acid; Arachidonic Acids; Blood Coagulation; Blood Platelets; Femoral Artery; Hyperlipidemias; Male; Partial Thromboplastin Time; Platelet Aggregation; Prostaglandins F; Prostaglandins H; Prothrombin Time; Rabbits; Thrombosis; Thromboxane B2