thromboxane-a2 and lauric-acid

In two studies we have compared the effects of four different saturated fat diets (medium chain fatty acids (MCFA), and lauric, myristic and palmitic acids) with those of a monounsaturated oleic acid diet on in-vitro whole blood aggregation in healthy women and men.. Study 1 had a cross-over design with three diet periods of each six weeks, and studied the effects of diets enriched in lauric, palmitic or oleic acids. Study 2 had a parallel design. After a three week oleic acid run-in diet, three groups of subjects were formed which consumed either an MCFA, myristic acid or oleic acid rich diet for six weeks.. Eighteen women and 14 men in Study 1 and 37 women and 23 men in Study 2. All subjects were healthy and were aged 20-60 y.. The experimental diets were the same in nutrient composition except for on average 8 En% (Study 1) or 10 En% (Study 2) which was provided by either MCFA, lauric acid, myristic acid, palmitic acid or oleic acid. Blood samples were taken at the end of each dietary period. Whole blood platelet aggregation, anticoagulated with recombinant hirudin was assessed after administration of collagen (final concentration (fc): 0.38 microgram/mL) in Study 1 and collagen (fc: 0.22 microgram/mL) or ADP (fc: 1.25 mumol/L) in Study 2. Collagen-induced formation of thromboxane (Tx)A2, measured as thromboxane (Tx)B2, was evaluated in Study 1 only.. The aggregation velocity between the saturated fatty acid diets and the monounsaturated fatty acid diet did not differ. TxB2 concentrations measured in collagen activated blood samples, which correlated significantly with aggregation velocity, did not differ between the lauric or the palmitic compared with the oleic acid diet. A stepwise regression analysis indicated that collagen-induced aggregation was negatively correlated with the number of red blood cells. ADP-induced aggregation also correlated negatively with red blood cell count, and positively with platelet count.. The exchange of 7-10 En% from oleic acid for MCFA, lauric, myristic or palmitic acid does not affect in-vitro whole blood aggregation induced by collagen. ADP-induced aggregation is not affected when 10 En% from oleic acid is exchanged for MCFA or myristic acid.

Topics: Adenosine Diphosphate; Adult; Anticoagulants; Collagen; Cross-Over Studies; Diet; Dietary Fats; Energy Intake; Fatty Acids; Female; Hirudins; Humans; Lauric Acids; Male; Middle Aged; Myristic Acid; Oleic Acid; Palmitic Acid; Platelet Aggregation; Recombinant Proteins; Thromboxane A2; Thromboxane B2

The present study compared the effects of diets rich in stearic acid (C18:0) versus one high in lauric and myristic acid (C12:0, C14:0) on platelet phospholipid fatty acid levels and concentrations of urinary thromboxane B2 (TXB2) and 6-keto-PGF1 alpha, which are stable metabolites of thromboxane A2 (TXA2) and PGI2 and indicators of cardiovascular hemostasis. A diet high in dairy butter (B) was the source of C12:0 and C14:0; C18:0 was provided by diets high in cocoa butter (CB), milk chocolate (CHOC) or CB+B in a 4:1 ratio (MIX). A randomized, crossover double-blind experimental design was used. Experimental subjects (n = 15) consumed each diet for 26 days, with a 1-month washout period between each experimental period. Urine and blood were collected from each subject at the beginning and end of each dietary period. Urinary TXB2 and 6-keto-PGF1 alpha were analyzed by radioimmunoassay (RIA). There were no effects of diet on the 24-hour excretion of either metabolite or on the ratio of 6-keto-PGF1 alpha/TXB2, even though there were significant changes in the eicosanoid precursor, arachidonic acid (C20:4n-6), in platelet phospholipids. C20:4n-6 levels increased (44.8% +/- 1.0% to 47.1% +/- 1.3%; P < .05) in the phosphatidylethanolamine phospholipid subclass in subjects on the B diet and decreased in the phosphatidylcholine subclass on the CB diet (16.5% +/- 1.0% to 14.2% +/- 1.1%; P < .05) compared with baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Blood Platelets; Butter; Cacao; Dietary Fats; Double-Blind Method; Epoprostenol; Fatty Acids; Humans; Infant, Newborn; Lauric Acids; Male; Myristic Acid; Myristic Acids; Phosphatidylcholines; Phosphatidylethanolamines; Stearic Acids; Thromboxane A2; Thromboxane B2

Antithrombotic effects of KW-3635, a newly synthesized thromboxane (TX) A2-receptor antagonist, were studied in guinea pigs. In the extracorporeal circulation thrombosis model, the shunt was filled with thrombi, and reduction of platelet count and increase in plasma TXA2 concentration were observed. KW-3635 (30 and 100 mg/kg, p.o.) inhibited the thrombus formation in the shunt and prevented the decrease in platelet count in the circulating blood without affecting the red blood cell count. BM13,505 (30, 100 mg/kg, p.o.), another TXA2-receptor antagonist, and ticlopidine (300 mg/kg, p.o.), an antiplatelet drug, also inhibited the thrombus formation, while aspirin (10, 300 mg/kg, p.o.) did not. Peripheral arterial occlusive disease was induced by injection of sodium laurate into the femoral artery in guinea pigs. Daily oral administration of KW-3635 (3-30 mg/kg) significantly prevented the progression of vascular lesions. BM13,505 (3-30 mg/kg, p.o.) and ticlopidine (100 mg/kg, p.o.) also ameliorated the vascular lesions, whereas aspirin (10, 100 mg/kg, p.o.) did not. KW-3635 at concentrations up to 10(-4) M did not affect coagulation parameters in vitro. These results suggest that TXA2 is involved in the pathogenesis of arterial thrombotic and ischemic disorders. KW-3635 may be useful for the treatment of thrombotic disease and peripheral arterial occlusive diseases.

Topics: Animals; Arterial Occlusive Diseases; Aspirin; Benzimidazoles; Benzoxepins; Blood Coagulation; Blood Platelets; Disease Models, Animal; Erythrocyte Count; Femoral Artery; Guinea Pigs; Lauric Acids; Male; Phenylacetates; Platelet Count; Sulfonamides; Thrombosis; Thromboxane A2; Thromboxanes; Ticlopidine