Tocotrienols-induced inhibition of platelet thrombus formation and platelet aggregation in stenosed canine coronary arteries.

Background: Dietary supplementation with tocotrienols has been shown to decrease the risk of coronary artery disease. Tocotrienols are plant-derived forms of vitamin E, which have potent anti-inflammatory, antioxidant, anticancer, hypocholesterolemic, and neuroprotective properties. Our objective in this study was to determine the extent to which tocotrienols inhibit platelet aggregation and reduce coronary thrombosis, a major risk factor for stroke in humans.

Activation of protein kinase-C differentially regulates insulin-like growth factor-I and basic fibroblast growth factor messenger RNA levels.

Fibroblasts represent one of the in vivo sites of insulin-like growth factor-I (IGF-I) production. In this study rat dermal fibroblasts in culture were used as a model system to assess the effect of activation of protein kinase-C on the levels of the mRNAs encoding IGF-I and another growth factor, basic fibroblast growth factor (bFGF). IGF-I and bFGF mRNA levels were determined using a solution hybridization/RNase protection assay.

Regulation of insulin-like growth factor I production in rat C6 glioma cells: possible role as an autocrine/paracrine growth factor.

The growth of rat glioma C6 cells, which provide an in vitro model of glial cells, is inhibited by retinoic acid and glucocorticoids, two agents which are important in brain differentiation and growth. To determine whether the growth-inhibitory effects of these agents are mediated by alterations in insulin-like growth factor I (IGF-I) production, the effects of retinoic acid and dexamethasone on IGF-I production and messenger RNA levels in C6 cells were investigated. IGF-I mRNA levels were determined using a solution hybridization/RNase protection assay.

Tissue-specific regulation of basic fibroblast growth factor mRNA levels by diabetes.

Because basic fibroblast growth factor (bFGF) is recognized as an angiogenic factor and diabetes is characterized by multiple vascular complications, including diabetic microangiopathy, we examined the regulation of tissue bFGF mRNA levels by diabetes. Diabetes was induced in male Sprague-Dawley rats by injection of 125 mg/kg body wt i.v.

Regulation of insulin-like growth factor I messenger ribonucleic acid levels by serum in cultured rat fibroblasts.

Fibroblasts represent one of the in vivo sites of extrahepatic insulin-like growth factor I (IGF-I) production. In this study, cultured fibroblasts prepared from the skin of neonatal rats were used as a model to assess the role of serum in regulating IGF-I messenger RNA (mRNA) levels. IGF-I mRNA, as demonstrated by Northern blot analysis, was present in the cultured fibroblasts, and serum free media which was conditioned by fibroblasts for 20 h contained 108 pg/ml of immunoreactive IGF-I.

Peroxide mediated effects of homocysteine on arterial prostacyclin synthesis.

The effects of homocysteine on the synthesis of arterial prostacyclin (PGI2) were investigated. Homocysteine at 10 mM and 1 mM concentration inhibited PGI2 synthesis from both exogenous and endogenous arachidonic acid. While concentrations of 100 microM and 1 microM stimulated PGI2 synthesis.

Triglyceride-lowering effect of dietary vitamin E in streptozocin-induced diabetic rats. Increased lipoprotein lipase activity in livers of diabetic rats fed high dietary vitamin E.

High vitamin E supplementation in the diets of streptozocin-induced diabetic rats eliminates accumulation of lipid peroxides in the plasma and the liver, returns the plasma triglycerides toward normal levels, and increases the activity of lipoprotein lipase. Vitamin E has no effect on the levels of insulin or glucose. These findings suggest that vitamin E increases the total hepatic triglyceride lipase activity by increasing the lipoprotein lipase activity possibly by protecting the membrane-bound lipase against peroxidative damage.

Production of 12-hydroxyeicosatetraenoic acid and vitamin E status in platelets from type I human diabetic subjects.

Vitamin E content and biosynthesis of 12-hydroxyeicosatetraenoic acid (12-HETE) have been measured in platelets from type I diabetic subjects and age- and sex-matched, nondiabetic control subjects. Platelets from diabetic subjects synthesized significantly greater quantities of 12-HETE than did platelets from control subjects when 12-HETE synthesis was induced by thrombin or collagen, either in the presence or absence of indomethacin. Platelet conversion of exogenously added arachidonic acid (AA) to 12-HETE was not significantly different between the diabetic and control groups in the absence of indomethacin, although a small but significant increase in the conversion of AA to 12-HETE was present in the diabetic group platelets when indomethacin was added to the reaction.

Prostaglandin response in the exercise conditioned rat.

Thrombin- and collagen-induced thromboxane A2 (TxA2) production were significantly reduced in washed platelets from exercise-trained rats as compared to sedentary controls. No consistant differences were found in the synthesis of prostacyclin (PGI2) from endogenous arachidonate in strips of aorta. Isolated hearts perfused by the "Langendorff" method respond to bolus injections of PGI2 with a decreased perfusion pressure.

Interrelation of platelet vitamin E and thromboxane synthesis in type I diabetes mellitus.

Platelet vitamin E content and thromboxane A2 (TxA2) synthesis have been investigated in type I diabetic subjects and age- and sex-matched controls. Platelets, but not plasma, from diabetic subjects contained significantly lower vitamin E levels and synthesized significantly greater amounts of TxA2 when challenged with collagen or thrombin than platelets from control subjects. Conversion of exogenously added arachidonic acid to TxA2 was unaltered between platelets from control and diabetic groups.

Influence of dietary vitamin E on platelet thromboxane A2 and vascular prostacyclin I2 in rabbit.

Rabbits were maintained on vitamin E-deficient and vitamin E-supplemented diets. Thrombin- and collagen-induced thromboxane A2 production were significantly elevated in vitamin E-deficient platelets. Conversion of arachidonic acid to platelet thromboxane A2 was unchanged between the two groups of animals.

Alterations of the prostacyclin-thromboxane ratio in streptozotocin induced diabetic rats.

Thrombin induced thromboxane A2 and prostaglandin E2 production were significantly increased in platelets of streptozotocin induced diabetic rats as compared to non-diabetic control rats, while collagen induced thromboxane A2 production was decreased. Using exogenous arachidonic acid, prostaglandin E2 production, but not thromboxane A2 production, was increased in platelets from streptozotocin treated animals. Prostacyclin production in the diabetic aorta was significantly lowered; however, control levels of prostacyclin production resulted after incubation of the tissue with dipyridamole.

Modulation of Platelet thromboxane A2 and arterial prostacyclin by dietary vitamin E.

Platelets from vitamin E-deficient and vitamin E-supplemented rats generate the same amount of thromboxane A2 (TxA2) when they are incubated with unesterified arachidonic acid. Platelets from vitamin E-deficient rats produced more TxA2 than platelets from vitamin E-supplemented rats when the platelets are challenged with collagen. Arterial tissue from vitamin E-deficient rats generates less prostacyclin (PGI2) than arterial tissue from vitamin E- supplemented rats.