linoleic-acid and Thrombosis

The cholesterol hypothesis implies that reducing the intake of saturated fatty acids and cholesterol and increasing that of polyunsaturated fatty acid are effective in lowering serum total cholesterol (TC), and thereby reducing the incidence of coronary heart disease (CHD). However, these dietary recommendations are essentially ineffective in reducing TC in the long run, but rather increase mortality rates from CHD and all causes. The reported "apparent relative risk of high TC in CHD mortality" (the ratio of mortality at the highest/lowest TC levels) varied several-fold among populations studied. The incidence of familial hypercholesterolemia (FH) in a population was proposed to be a critical factor in the observed variability, which could be accounted for by assuming that 1) the high CHD mortality rate in high-TC groups is mainly a reflection of the incidence and severity of FH, and 2) high TC is not a causative factor of CHD in non-FH cases. This interpretation is supported by recent observations that high TC is not positively associated with high CHD mortality rates among general populations more than 40-50 years of age. More importantly, higher TC values are associated with lower cancer and all-cause mortality rates among these populations, in which relative proportions of FH are likely to be low (circa 0.2%). Although the effectiveness of statins in preventing CHD has been accepted in Western countries, little benefit seems to result from efforts to limit dietary cholesterol intake or to TC values to less than approximately 260 mg/dl among the general population and the elderly. Instead, an unbalanced intake of omega6 over omega3 polyunsaturated fats favors the production of eicosanoids, the actions of which lead to the production of inflammatory and thrombotic lipid mediators and altered cellular signaling and gene expression, which are major risk factors for CHD, cancers, and shorter longevity. Based on the data reviewed here, it is urgent to change the direction of current cholesterol-related medication for the prevention of CHD, cancer, and all-cause mortality.

Topics: alpha-Linolenic Acid; Anticholesteremic Agents; Atherosclerosis; Coronary Disease; Docosahexaenoic Acids; Eicosapentaenoic Acid; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemia Type II; Inflammation; Inflammation Mediators; Linoleic Acid; Neoplasms; Risk Factors; Thrombosis

Platelets take part in haemostasis and thrombosis, and studies have been carried out to try to understand how dietary fatty acids could reduce platelet activation and thus the risk of cardiovascular disease. Unfortunately, many of these studies had serious methodological flaws, and the shortcomings in their study designs are probably the main reason for contradictory results in humans. The evidence concerning linoleic acid is not consistent, but intervention studies show increased platelet aggregation to various agonists after high-linoleic-acid diets. On the other hand, intake of alpha-linoleic acid either has no effect or leads to decreased platelet aggregation when compared with linoleic acid. High intake of long-chain n-3 fatty acids of fish or fish oils seems to usually decrease platelet aggregation. To date, there have not been many studies on the effect of platelet aggregation of small or reasonable amounts of n-3 fatty acids.

Topics: alpha-Linolenic Acid; Coronary Disease; Dietary Fats, Unsaturated; Fatty Acids, Omega-3; Fish Oils; Humans; Linoleic Acid; Linoleic Acids; Plant Oils; Platelet Aggregation; Platelet Aggregation Inhibitors; Thrombosis

Dietary experiments, performed in metabolic wards, gave rise to predictive regression equations relating changes of plasma cholesterol concentration to the intake of fatty acids of the diet. It has been established that polyunsaturated fatty acids diminish and most saturated fatty acids increase plasma cholesterol concentration. This information led to expect that dietary use of palm oil may induce an unfavorable plasma lipoprotein profile. This has not been the case as shown in various dietary experiments. The reasons for this discrepancy is discussed. The influence of palm oil enriched diets on prothrombotic variables show that platelets are not affected in their function during prolonged dietary intervention. It is important to continue research on the effects of palm oil based diet on plasma fibrinogen, factor VII. There is still discordant information in this field.

Topics: Adult; Animals; Arteriosclerosis; Child; Cholesterol; Diet, Atherogenic; Dietary Fats; Factor VII; Feeding Behavior; Female; Fibrinogen; Fish Oils; Humans; Hypercholesterolemia; Linoleic Acid; Linoleic Acids; Lipoproteins; Male; Palm Oil; Plant Oils; Platelet Aggregation; Rabbits; Rural Population; Sunflower Oil; Thrombosis; Triglycerides; Urban Population; Venezuela

Topics: Animals; Blood Platelets; Endothelium, Vascular; Fatty Acids; Fibrinolytic Agents; Humans; Linoleic Acid; Linoleic Acids; Lipoxygenase; Platelet Aggregation Inhibitors; Thrombosis

Topics: alpha-Linolenic Acid; Animals; Arteriosclerosis; Blood Platelets; Diabetes Complications; Dietary Fats; Fatty Acids; Fatty Acids, Unsaturated; Humans; Hyperlipoproteinemias; Linoleic Acid; Linoleic Acids; Linolenic Acids; Nutritional Physiological Phenomena; Thrombosis

Topics: 8,11,14-Eicosatrienoic Acid; Animals; Arachidonic Acid; Arachidonic Acids; Arteriosclerosis; Blood Platelets; Dietary Fats; Eicosanoic Acids; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Unsaturated; Humans; Linoleic Acid; Linoleic Acids; Linolenic Acids; Platelet Aggregation; Prostaglandins; Thrombin; Thrombosis

Atrial fibrillation significantly increases the risk of thromboembolism and stroke. Wenxin Keli (WXKL) is a widely used Chinese patent medicine against arrhythmia but if it has antithrombotic activity is unknown. Since platelet activation is a critical factor in thrombosis and the key target for many antithrombotic drugs, this study aims to demonstrate the antithrombotic efficacy of WXKL. In vitro platelet activation experiments showed that WXKL significantly inhibited platelet adhesion and aggregation. The potential active monomers in WXKL were screened by in silico prediction and in vitro platelet aggregation/adhesion assays. From WXKL chemical fractions and more than 40 monomers, linoleic acid (LA) was identified as the strongest antiplatelet compound. Oral administration of WXKL (1.2 g/kg/day) and LA (50 mg/kg/day) for 7 days significantly improved FeCl3-induced carotid thrombus formation in ICR mice without prolonging bleeding time. Flow cytometry showed that both WXKL and LA inhibited the release of p-selectin after platelet activation. ELISA showed that WXKL and LA also inhibited the expression of 6-Keto-PGF1α in plasma of mice with thrombus, but had no obvious effect on the expression of TXB2. WXKL inhibited platelet activation by broadly inhibiting the phosphorylation of protein kinase B (Akt), mitogen-activated protein kinases (MAPKs) and phospholipase C (PLC) β3. In contrast, LA only inhibited the phosphorylation of PLCβ3. In conclusion, WXKL and its active component LA showed good antiplatelet and antithrombotic efficacy in vivo and in vitro. Mechanistically, the multicomponent Chinese medicine WXKL acts on multiple targets in the platelet activation pathway whereas its active monomer linoleic acid acts specifically on phospholipase C β3.

Topics: Animals; Atrial Fibrillation; Drugs, Chinese Herbal; Fibrinolytic Agents; Linoleic Acid; Mice; Mice, Inbred ICR; P-Selectin; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Thrombosis

The current study was to evaluate the anti-thrombotic effect of alpha-linolenic acid (ALA) which was isolated and purified from Jiaomu in vivo.. The seeds were crushed and subsequently subjected to saponification, acid hydrolysis, gradient freezing, urea inclusion and complexation of silver nitrate to obtain the unsaturated fatty acids. The chemical characteristics of isolated ALA were validated by 1HNMR, 13CNMR and mass spectrometry, and then the anti-thrombotic effect of ALA and its mixture with linoleic acid (1:1) were evaluated in the following experiments.. The alpha-linolenic acid was isolated and purified from Jiaomu through our newly established methods. ALA and its mixture with linoleic acid can prolong the hemorrhage and coagulation time as well as enhanced the survival rate of mice subjected to collagen-adrenaline induced thrombosis. In addition, the thrombosis on A-V bypass and platelet aggregation of rats will be reduced after treated with ALA or its mixture, and the expression level of Akt and PI3K protein decreased 26% and 31%, respectively.. We designed and optimized a very simple and high-yield procedure to isolate ALA and linoleic acid mixture from seeds of Zanthoxylum bungeanum Maxim and demonstrated that such mixture can obtain a good anti-thrombotic effect through the modulation of PI3K/Akt signaling.

Topics: alpha-Linolenic Acid; Animals; Fibrinolytic Agents; Humans; Linoleic Acid; Male; Mice; Phosphatidylinositol 3-Kinases; Platelet Aggregation; Proto-Oncogene Proteins c-akt; Rats; Seeds; Thrombosis; Zanthoxylum

Topics: Animals; Carcinoma 256, Walker; Cell Communication; Dietary Fats; Epoprostenol; Humans; Hydroxyeicosatetraenoic Acids; Inflammation; Linoleic Acid; Linoleic Acids; Neoplasm Metastasis; Rats; Rats, Wistar; Thrombosis

To study the influence of dietary fatty acids on arterial thrombosis tendency 65 groups of male rats were fed diets containing 50% of their digestible energy as fat from 32 different oils and fats. After 8 weeks their arterial thrombosis tendency was assessed by measuring the obstruction time (OT) of a loop-shaped polythene cannula inserted into the abdominal aorta. Using multiple regression analysis log10 OT was modelled as a function of the relative amounts of the various dietary fatty acids and their combinations. The best fit (R2 = 0.79) was obtained for the sums of all monoenoic and (n-6) and (n-3) polyenoic fatty acids, which appeared antithrombotic. The fit for the sum of all saturated fatty acids, which had a prothrombotic effect, was almost as good (R2 = 0.76). The ratio between dietary polyunsaturated and saturated fatty acids (P:S ratio) appeared a strong predictor of arterial thrombosis tendency (R2 = 0.77). Marine oils did not have a more powerful antithrombotic effect than could be expected on the basis of their P:S ratios. Using stepwise regression analysis myristic acid, 14:0, was shown to be the strongest prothrombotic fatty acid whereas linoleic acid, 18:2(n-6), was the strongest antithrombotic fatty acid. Since the number of marine oils was very limited the effects of the 'fish fatty acids' eicosapentaenoic acid, 20:5(n-3) and docosahexaenoic acid, 22:6(n-3), on arterial thrombus formation could not be tested reliably. The same appeared true for gamma-linolenic acid, 18:3(n-6), and stearidonic acid, 18:4(n-3), present in a few vegetable oils only.

Topics: Animals; Arterial Occlusive Diseases; Dietary Fats; Dietary Fats, Unsaturated; Disease Models, Animal; Energy Intake; Fatty Acids; Fatty Acids, Unsaturated; Fish Oils; Linoleic Acid; Linoleic Acids; Male; Myristic Acid; Myristic Acids; Rats; Rats, Wistar; Regression Analysis; Thrombosis

Topics: alpha-Linolenic Acid; Animals; Arteriosclerosis; Coronary Disease; Dietary Fats, Unsaturated; Fatty Acids, Essential; Humans; Infant, Newborn; Linoleic Acid; Linoleic Acids; Lipoproteins, LDL; Thrombosis

This study was designed to determine whether dietary linoleate and all-rac-alpha-tocopheryl acetate (vitamin E) interact to affect serum thromboxane A2 (TXA2) and prostacyclin (PGI2) status and therefore, thrombogenic potential. 6 groups of 12 weanling male Sprague-Dawley rats were fed semipurified diets containing 11 or 18% of energy from linoleate and 0, 100 or 5000 mg vitamin E/kg diet for 10 weeks. Platelet and serum alpha-tocopherol concentrations increased logarithmically with increasing dietary vitamin E. Serum TXA2, measured as TXB2, platelet arachidonate and thiobarbituric acid reactive substances were significantly greater in the vitamin E deficient groups than in groups receiving vitamin E (p < 0.05). Serum PGI2 levels, determined as 6-keto-PGF1 alpha, were not affected by diets. No interaction was found between dietary linoleate and vitamin E. However, vitamin E supplementation produced significantly less serum TXB2 than did vitamin E deficient diets (p < 0.05). Vitamin E deficiency may be prothrombogenic by increasing platelet arachidonate, lipid peroxidation and serum TXA2 levels while vitamin E supplementation at levels used in this study may decrease such effects.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Blood Platelets; Epoprostenol; Linoleic Acid; Linoleic Acids; Lipid Peroxidation; Male; Rats; Rats, Sprague-Dawley; Thiobarbituric Acid Reactive Substances; Thrombosis; Thromboxane A2; Thromboxane B2; Vitamin E; Vitamin E Deficiency

The 15-omega-lipoxygenase enzyme in endothelial cells metabolizes endogenous linoleic acid (18:2) into 13-hydroxyoctadecadienoic acid (13-HODE) under basal conditions, i.e., in unstimulated endothelial cells. 13-HODE is thought to regulate the non-adhesivity of the endothelium, contributing to vessel wall/blood cell biocompatibility. We performed experiments, therefore, to determine the relationship between basal levels of cAMP, 13-HODE synthesis, and platelet/endothelial cell adhesion. We found that 13-HODE synthesis increased with elevated cAMP levels and that the elevated 13-HODE levels correlated with increased 18:2 turnover in the triacylglycerol pool. In contrast, neither 18:2 nor arachidonic acid (20:4) turnover in the phospholipid nor prostacyclin (PGI2) production were changed with elevated cAMP levels. Platelet/endothelial cell adhesion was inversely proportional to 13-HODE synthesis. We conclude that intracellular 13-HODE influences platelet/vessel wall interactions, is synthesized from 18:2 released from the endogenous triacylglycerol pool, and that this pathway is modulated by intracellular cAMP levels.

Topics: Arachidonic Acid; Arachidonic Acids; Cell Adhesion; Cells, Cultured; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Cyclic AMP; Endothelium, Vascular; Humans; Linoleic Acid; Linoleic Acids; Phospholipids; Platelet Adhesiveness; Thrombosis; Triglycerides

Topics: Anticoagulants; Arteriosclerosis; Biomedical Research; Fatty Acids; Fatty Acids, Essential; Linoleic Acid; Preventive Medicine; Thrombosis