8-11-14-eicosatrienoic-acid and Arteriosclerosis

Topics: 8,11,14-Eicosatrienoic Acid; Adult; Arteriosclerosis; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Humans; Hyperlipoproteinemia Type II; Male; Middle Aged

Topics: 8,11,14-Eicosatrienoic Acid; Animals; Arteriosclerosis; Blood Platelets; Blood Vessels; Dietary Fats; Eicosapentaenoic Acid; Epoprostenol; Fatty Acids, Unsaturated; Hemostasis; Humans; Lipid Peroxides; Mitogens; Platelet Activating Factor; Platelet Aggregation; Thromboxanes

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

Dihomo-gamma-linolenic acid ( DHLA ), a precursor of monoenoic anti-aggregatory prostaglandins (PGE1, PGD2), was administered for 4 weeks in a daily dose of 1.0 g into 33 patients with atherosclerosis on a basis of a double-blind trial. Comparison of treatment and placebo groups revealed elevation of DHLA in red cell lipids in DHLA -treated subjects. No differences, however, between the two groups could be observed in platelet aggregability, thromboxane A2 generation by platelets, serum cholesterol, PGE1 and PGE2 levels, and in inhibitory activity of low-density lipoproteins against prostacyclin synthetizing system in arteries. The dietary supplementation used did not lead to distinct antithrombotic effects.

Topics: 8,11,14-Eicosatrienoic Acid; Adult; Aged; Arteriosclerosis; Blood Glucose; Cholesterol; Dinoprostone; Epoprostenol; Fatty Acids, Unsaturated; Humans; Lipids; Lipoproteins, LDL; Male; Middle Aged; Platelet Aggregation; Prostaglandins E; Thromboxane A2

Oxidized low-density lipoprotein (oxLDL) is an important risk factor for vascular injury. Its role on coronary vasoconstriction remains speculative. Endothelial monooxygenases (cytochrome P450s [CYPs]) are regulators of vascular tonus through production of epoxy fatty acids. We investigated the effects of oxLDL on CYP monooxygenases in human arterial coronary endothelial cells and explanted healthy and atherosclerotic aortae. We found oxLDL to induce radical oxygen species production via the action of NADPH oxidase NOX4. Intracellular radical oxygen species production prompted reduced protein expression of the transcriptional regulator nuclear factor 1 (NF-1). We identified novel DNA binding sites for NF-1 in promoter regions of CYPs. DNA binding of NF-1 was confirmed by electromobility shift assays. OxLDL repressed DNA binding of NF-1 and diminished transcript level of CYP genes targeted by this factor. The production of endothelial-derived hyperpolarization factor, a key regulator of vascular tonus, was also reduced. Repression of CYP monooxygenases was reversed, and production of endothelial-derived hyperpolarization factor was normalized after treatment of endothelium with the lectin-like oxLDL receptor antagonist kappa-carrageenan or blocking of LOX-1 with a specific antibody. This suggests a mechanistic role of CYP monooxygenases in oxLDL-induced vascular injury. Therapy of endothelial dysfunction through LOX-1 receptor antagonism will be an interesting avenue to explore. The full text of this article is available online at http://www.circresaha.org.

Topics: 8,11,14-Eicosatrienoic Acid; Arteriosclerosis; Blotting, Western; Carrageenan; Cells, Cultured; Coronary Vessels; Cytochrome P-450 Enzyme System; Electrophoretic Mobility Shift Assay; Endothelium, Vascular; Epoxide Hydrolases; Humans; Lipoproteins, LDL; Malondialdehyde; Nitric Oxide; Promoter Regions, Genetic; Reactive Oxygen Species; Receptors, LDL; Receptors, Oxidized LDL; Scavenger Receptors, Class E; Transcription, Genetic; Vascular Diseases

To prospectively investigate the relation of plasma cholesterol ester (CE) and phospholipid (PL) fatty acid (FA) composition with incidence of coronary heart disease (CHD).. 3,591 white participants in the Minneapolis field center of the Atherosclerosis Risk in Communities Study, aged 45-64 years, were studied. Plasma FA composition of CEs and PLs was quantified using gas-liquid chromatography and expressed as percentage of total FAs. Incident CHD was identified during 10.7 years of follow-up. In both CE and PL fractions, the proportions of stearic (18:0) acid, dihomo-gamma-linolenic (20:3n6) acid and total saturated fatty acids (SFAs) were significantly higher while arachidonic (20:4n6) acid and total polyunsaturated fatty acids (PUFAs) were significantly lower among participants who developed incident CHD (n = 282). After adjusting for age, gender, smoking, alcohol drinking, sports activity, and non-FA dietary factors, the incidence of CHD was significantly and positively associated with the proportion of dihomo-gamma-linolenic acid but inversely associated with arachiadonic acid. The multiply-adjusted rate ratios (RRs) of CHD incidence for the highest versus the lowest quintile were 1.31 in CE and 1.44 in PL for dihomo-gamma-linolenic acid (p for trend: 0.05 and 0.017, respectively), 0.59 in CE and 0.65 in PL for arachidonic acid (p: 0.016 and 0.024, respectively). Also significantly and positively associated with incident CHD were PL stearic acid and CE linolenic (18:3n3) acid. Only a borderline significant positive association was observed for total SFAs in CE (multivariate RRs across quintiles: 1.00, 1.15, 1.40, 1.62, 1.32; p = 0.07). Total PUFAs or monounsaturated FA were not independently associated with CHD.. Our study found a weak positive association of SFAs with incident CHD. Our findings also confirm that FA metabolism in the body, such as the activity of delta-5 desaturase, which converts dihomo-gamma-linolenic acid to arachidonic acid, may affect the development of CHD.

Topics: 8,11,14-Eicosatrienoic Acid; Arachidonic Acid; Arteriosclerosis; Cholesterol Esters; Cohort Studies; Coronary Disease; Fatty Acids, Unsaturated; Female; Health Surveys; Humans; Male; Middle Aged; Phospholipids; Prospective Studies; Risk Factors; Stearic Acids

Studies in man and laboratory animals suggest that omega 3 polyunsaturated fatty acid constituents of fish oils have antiatherosclerotic properties. We have studied the effects of several such polyunsaturated fatty acids for ability to modify the in vitro release of mitogens from human platelets. Such mitogens may produce the fibro-proliferative component of atherosclerotic plaques. Both 5,8,11,14,17-eicosapentaenoic acid (20:5 omega 3) and 4,7,10,13,16,19-docosahexaenoic acid (22:6 omega 3), major constituents of fish oils, inhibited adenosine diphosphate-induced aggregation of platelets and the accompanying release of mitogens. These effects are dose dependent. Linolenic acid (18:3 omega 3), the biosynthetic precursor of eicosapentaenoic acid, also inhibited platelet aggregation and mitogen release. Eicosapentaenoic acid also inhibited mitogen release from human monocyte-derived macrophages, which, in vivo, are an additional source of mitogens during atherogenesis. Potent inhibition of human platelet aggregation and mitogen release was also seen with dihomo-gamma-linolenic acid (8,11,14-eicosatrienoic acid 20:3 omega 6), whose levels are reportedly elevated in Eskimos subsisting on marine diets. We conclude that diets that elevate plasma and/or tissue levels of eicosapentaenoic acid, docosahexaenoic acid and dihomo-gamma-linolenic acid precursor gamma-linolenic acid (18:3 omega 6) may exert antiatherosclerotic effects by inhibiting the release of mitogens from platelets and other cells.

Topics: 8,11,14-Eicosatrienoic Acid; Adult; Arachidonic Acid; Arachidonic Acids; Arteriosclerosis; Blood Platelets; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Female; Growth Inhibitors; Growth Substances; Humans; Inuit; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors

Topics: 8,11,14-Eicosatrienoic Acid; Arteriosclerosis; Diabetes Mellitus, Type 1; Epoprostenol; Fatty Acids, Unsaturated; Humans; Lipids; Platelet Aggregation

Prostaglandins are synthesized from eicosa-8,11,14-trienoic acid and eicosa-5,8,11-14-tetraenoic acid by smooth muscle cell cultures from guinea pig aorta. Production is inhibited by indomethacin. The precursor fatty acids and their prostaglandin derivatives inhibit proliferation of the cell cultures. The relative availability of fatty acids for prostaglandin biosynthesis may represent a control mechanism for cell proliferation.

Topics: 8,11,14-Eicosatrienoic Acid; Aorta; Arachidonic Acids; Arteriosclerosis; Cell Division; Cholesterol Esters; Fatty Acids, Unsaturated; Muscle, Smooth; Prostaglandins E