thromboxane-a2 and Hyperlipoproteinemias

There is abundant evidence that changes in diet and various types of vessel wall injury can independently induce the growth of arterial lesions in experimental animals. These lesions closely resemble those found in humans with atherosclerosis. Whether endothelial injury or accumulation of lipoprotein in the arterial intima is the initial event, the progression of the disease is characterized by changes in the neointima that favor the deposition of lipid. The metabolism of proteoglycans may be especially important in this process; this is relevant to diabetes because changes in proteoglycan metabolism are associated with this disease. Insulin and growth hormone may favor the proliferation of smooth muscle cells in the arteries of diabetic patients. Many agents, which are potentially injurious to the endothelium, accentuate the response of the vessel wall to injury. Modifications of the thrombotic process, such as increased production of thromboxane by platelets, decreased production of prostacyclin by the endothelium, and increased production of von Willebrand factor further enhance the thrombotic process and may be important in the initiation and subsequent progression of atherosclerosis in diabetics. Alterations in lipoprotein metabolism may also facilitate the development of endothelial injury.

Topics: Animals; Arteries; Arteriosclerosis; Blood Platelets; Diabetes Complications; Diabetes Mellitus; Glycosaminoglycans; Humans; Hyperlipoproteinemias; Lipoproteins; Rabbits; Thromboxane A2

Tocotrienols, lipid-soluble antioxidants with vitamin E activity, have been reported to lower LDL-cholesterol concentrations and platelet aggregation in men, but results are contradictory.. To examine in detail the effects of a vitamin E concentrate rich in tocotrienols on serum lipoproteins and on platelet function in men at risk for cardiovascular disease.. In this randomized, double-blind, placebo-controlled parallel trial, 20 men received daily for 6 wk 4 capsules, each containing 35 mg tocotrienols and 20 mg alpha-tocopherol; 20 other men received 4 capsules daily, each providing 20 mg alpha-tocopherol. All men had concentrations of serum total cholesterol between 6.5 and 8.0 mmol/L or lipoprotein(a) concentrations > 150 mg/L.. Compliance was confirmed by changes in serum tocopherol and tocotrienol concentrations. Serum LDL cholesterol in the tocotrienol group was 4.80 mmol/L before and 4.79 mmol/L after intervention, and increased from 4.70 to 4.86 mmol/L in the placebo group (95% CI for the difference: -0.54, 0.19 mmol/L; P = 0.333). Also, changes in HDL cholesterol, triacylglycerol, lipoprotein(a), and lipid peroxide concentrations did not differ between the groups. After adjustment for differences in initial values, no effects were found on collagen-induced platelet aggregation velocity, maximum aggregation, or thromboxane B2 formation in citrated whole blood. ATP release, however, was lower in the tocotrienol group. Urinary thromboxane B2 and 11-keto-thromboxane B2 concentrations and coagulation and fibrinolytic measures did not change.. The tocotrienol supplements used had no marked favorable effects on the serum lipoprotein profile or on platelet function in men with slightly elevated lipid concentrations.

Topics: Adenosine Triphosphate; Adult; Blood Coagulation; Double-Blind Method; Fibrinolysis; Humans; Hypercholesterolemia; Hyperlipoproteinemias; Lipids; Lipoproteins; Male; Middle Aged; Palm Oil; Plant Oils; Platelet Aggregation; Thromboxane A2; Vitamin E

In a placebo-controlled trial healthy volunteers and patients with hyperlipoproteinemias types II and IV received orally vitamin E at doses of 300 mg and 600 mg daily for 2 weeks. Serum tocopherol levels increased two-fold, but serum concentrations of total lipids, cholesterol, triglycerides, ceruloplasmin and transferrin remained unchanged. Dietary supplementation with vitamin E suppressed elevated concentrations of plasma lipid peroxides and this effect was correlated with an increase in serum antioxidant activity. In patients a mild platelet suppressant effect of vitamin E (600 mg daily) was observed. Feeding an atherogenic diet to rabbits for a week resulted in elevation of plasma lipid peroxides and a 90% decrease in arterial generation of prostacyclin. Enrichment of the atherogenic diet with 100 mg vitamin E daily prevented the increase in plasma lipid peroxides and protected the prostacyclin generating system in arteries. Thus, in hyperlipoproteinemias vitamin E corrects certain abnormalities of lipid metabolism which might predispose to atherosclerosis.

Topics: Adult; Animals; Blood Platelets; Ceruloplasmin; Cholesterol; Diet, Atherogenic; Epoprostenol; Female; Humans; Hyperlipoproteinemias; Lipid Peroxides; Male; Middle Aged; Oxygen; Platelet Aggregation; Rabbits; Thromboxane A2; Transferrin; Triglycerides; Vitamin E