gamma-linolenic-acid and Arteriosclerosis

epidemiological studies suggest polyunsaturated fatty acids protect against the development of atherosclerosis. The aim of this study was to perform a randomized controlled trial of gamma-linolenic and eicosapentaenoic acids in patients with lower limb atherosclerosis. Main outcome measures were: cholesterol and lipoprotein concentrations; haemostatic and rheological variables; the ankle brachial pressure index; walking distance; and cardiovascular events and death.. 120 men and women with stable intermittent claudication were randomized to 2 years treatment with either a combination of gamma-linolenic and eicosapentaenoic acids, or placebo.. 39 (65.0 cent) of those taking fatty acids and 36 (60.0 cent) of those taking placebo completed the trial. Lipid concentrations did not differ significantly during the trial. In those taking fatty acids, haematocrit was significantly higher than in the placebo group after 6 months (46.1 cent compared with 44.6 cent, P 0.05).. a combination of polyunsaturated fatty acids produced a statistically significant reduction in systolic blood pressure, but no other significant benefits on risk factors. The trend towards fewer coronary events in those taking fatty acids warrants further investigation.

Topics: Aged; Arteriosclerosis; Blood Pressure; Dietary Supplements; Eicosapentaenoic Acid; Female; gamma-Linolenic Acid; Humans; Intermittent Claudication; Male; Surveys and Questionnaires; Treatment Outcome

Effects of a dietary intake of the polyunsaturated omega-6 essential fatty acids (EFAs) linoleic and gamma-linolenic acids (GLA) on blood lipids, platelet function, and vascular prostacyclin production were studied 12 hyperlipidemic patients (doses of 3 g/day) and 12 male Wistar rats (doses of 3 mg/kg/day) for 4 months. In humans, GLA supplementation decreased plasma triglyceride (TG) levels by 48% (p < 0.001) and increased HDL-cholesterol concentration by 22% (p < 0.01). Total cholesterol and LDL-cholesterol levels were significantly decreased by omega-6 EFAs. Platelet aggregation induced by low concentrations of adenosine diphosphate (ADP) and epinephrine, and serum thromboxane B2 decreased by 45% both in humans and animals after GLA supplementation. Bleeding time increased 40% (p , 0.01). In rats, vascular prostacyclin production measured by radioimmunoassay of 6-keto-PGF1 alpha was enhanced by GLA intake. These effects of omega-6 EFAs may contribute to cardiovascular protection and prevention of the atherosclerotic disease.

Topics: 6-Ketoprostaglandin F1 alpha; Adenosine Diphosphate; Animals; Arteriosclerosis; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dietary Fats, Unsaturated; Epinephrine; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; gamma-Linolenic Acid; Humans; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Rats; Rats, Wistar; Thromboxane B2; Triglycerides

The present study was conducted to evaluate the antiatherogenic effects of dietary gamma-linolenic acid (GLA) (primrose oil) in apolipoprotein E (apoE) genetic knockout mice. Five-wk-old male mice were fed cholesterol-free diets containing 10 g/100 g lipid as corn oil (CO) [control diet, 0 mol/100 mol GLA and (n-3) polyunsaturated fatty acids (PUFA)], primrose oil (PO, 10 mol/100 mol GLA), fish oil-CO mix [FC; 9:1 wt/wt, 0 mol/100 mol GLA and 17 mol/100 mol (n-3) PUFA] or fish oil-PO mix [FP, 1:3 wt/wt, 8 mol/100 mol GLA and 5 mol/100 mol (n-3) PUFA] for 15 wk. Subsequently, diets were supplemented with cholesterol (1.25 g/100 g) and sodium cholate (0.5 g/100 g) and fed for an additional 10 and 16 wk. Plasma cholesterol and triglyceride levels generally did not differ among groups at 20, 30 and 36 wk of age. Mice fed GLA-containing diets (PO and FP) had significantly (P < 0.05) higher liver phospholipid levels of dihomo-gamma-linolenic acid, the elongated product of GLA, relative to CO and FC groups. Consumption of GLA (PO and FP diets) significantly reduced (P < 0.05) aortic vessel wall medial layer thickness at 20 and 30 wk. A parallel GLA-dependent suppression in the number of proliferating (proliferating cell nuclear antigen positive) aortic smooth muscle cells was also observed. Diets containing either GLA or (n-3) PUFA reduced (P < 0.05) atherosclerotic lesion size in 30-wk-old mice. These results indicate that dietary GLA can suppress smooth muscle cell proliferation in vivo and retard the development of diet-induced atherosclerosis in apoE knockout mice.

Topics: Animals; Aorta, Thoracic; Apolipoproteins E; Arteriosclerosis; Cell Division; Cells, Cultured; Cholesterol; Dietary Fats, Unsaturated; Fatty Acids; Fatty Acids, Essential; gamma-Linolenic Acid; Linoleic Acids; Liver; Male; Mice; Mice, Knockout; Muscle, Smooth, Vascular; Oenothera biennis; Phospholipids; Plant Oils; Triglycerides

Data from our in vitro studies indicate that macrophages isolated from mice fed GLA-enriched diets inhibit vascular SMC proliferation via a PGE1-cAMP dependent mechanism. Since SMC proliferation is one of the main events implicated in the pathogenesis of atherosclerosis (Ross, 1993), this anti-proliferative effect observed by dietary GLA is noteworthy. In vivo studies have established that dietary GLA is capable of retarding the atherosclerotic lesion formation in ApoE knock out mice, an animal model that develops atherosclerosis similar to humans (Reddick, 1994). We propose that dietary GLA has the potential to inhibit SMC proliferation leading to retardation of atherosclerotic lesion formation, and therefore favorable modulation of the atherogenic process.

Topics: Alprostadil; Animals; Arteriosclerosis; Cell Communication; Cell Division; Cells, Cultured; Coculture Techniques; Cyclic AMP; Dietary Fats, Unsaturated; DNA; gamma-Linolenic Acid; Humans; Macrophages; Mice; Models, Biological; Muscle, Smooth, Vascular

Evening primrose oil (Oenothera biennis) is a rich source of omega-6 series fatty acids. We report here the effects of dietary supplementation with evening primrose oil (EPO) on platelet aggregation as the main factor in arterial thrombus formation in an experimental model of atherogenesis in rabbits. A total of 40 male white New Zealand rabbits were divided into four groups (n = 10 animals/group): 1: normal diet, 2: atherogenic diet (ATD), 3: normal diet enriched with 15% EPO, 4: ATD + EPO. Each group was kept on the diet for 6 weeks. We determined serum lipid profile, platelet aggregation in whole blood, platelet thromboxane B2 production and platelet lipid peroxides. The atherogenic diet increased platelet aggregation (135% when ADP was used, and 185% when collagen was used as the inducer). Evening primrose oil reduced hyperaggregation to the values obtained in rabbits fed with the normal diet. Thromboxane synthesis was increased from 0.18 to 2.28 nmol/10(9) platelets); EPO reduced this value to 1.38 nmol/10(9) platelets. Lipid peroxides were increased by ATD from 0.27 to 0.81 nmol/10(8) platelets; EPO prevented this increase (0.35 nmol/10(8) platelets). In conclusion, EPO reduced platelet hyperaggregability in rabbits fed an atherogenic diet.

Topics: Animals; Arteriosclerosis; Diet, Atherogenic; Fatty Acids, Essential; gamma-Linolenic Acid; Linoleic Acids; Male; Oenothera biennis; Plant Oils; Platelet Aggregation; Rabbits; Thrombosis

To compare the atherogenecity of different fats and oils, a total of forty, 40-day-old male Japanese quails were fed one of the following diets for three months: basal diet (control), a diet-containing 15% corn oil (CO) and 2% cholesterol (CH), a diet-containing 15% oleic acid (OL) and 2% CH, a diet-containing 15% perilla oil (PE) and 2% CH, a diet-containing 15% evening [corrected] primrose oil (PR) and 2% CH. A higher plasma cholesterol concentration was found in the birds in the CO and OL groups, whereas the PE and PR groups showed a much lower level of plasma cholesterol than the CO and OL groups. In proportion to the increased plasma cholesterol, both CO and OL groups showed narrowing of the lumen of the ascending aorta and its large branches due to marked lipid-rich intimal thickening. Ultrastructural changes in the ascending aorta and its large branches were correlated with the degree of intimal thickening. The major foam cell types were macrophages and fibroblastic cells. The PE and PR groups showed the fewest lipid-rich intimal thickening lesions in their ascending aorta and its large branches. These findings suggest that the alpha-linolenic acid contained in perilla oil is less atherogenic than oleic and linoleic acid, and gamma-linolenic acid contained in evening [corrected] primrose oil has a tendency to decrease the plasma lipid level.

Topics: alpha-Linolenic Acid; Animals; Aorta; Aortic Diseases; Arteriosclerosis; Cholesterol Esters; Corn Oil; Coturnix; Dietary Fats; Dietary Fats, Unsaturated; Endothelium, Vascular; Fatty Acids, Essential; gamma-Linolenic Acid; Linoleic Acids; Lipids; Liver; Male; Microscopy, Electron; Muscle, Smooth, Vascular; Oenothera biennis; Organ Size; Plant Oils; Triglycerides

1. The present study was performed to determine whether chronic treatments with gamma linolenic acid (n-6, GLA) or eicosapentaenoic acid (n-3, EPA) would alter serum and red blood cell (RBC) unsaturated fatty acid composition, and to determine whether these treatments would affect blood pressure (BP), serum lipid metabolism and the development of atherosclerosis in spontaneously hypertensive rats (SHR). 2. To compare the effects on atherosclerosis, some SHR were denuded of aortic endothelium so that the development of atherosclerosis would be accelerated. Olive oil (control), GLA or EPA (low dose: 5 mg/day per rat, high dose: 50 mg/day per kg, respectively) was administered intraperitoneally for 6 weeks in SHR. 3. GLA treatments increased GLA and its metabolite, dihomo-GLA, levels in serum but not in RBC, while EPA treatments increased EPA level both in serum and in RBC. 4. The BP of control SHR was further elevated. EPA significantly reduced this elevation of systolic, mean and diastolic pressure within the first week and thereafter, whereas GLA did not affect BP elevation. Neither heart rate or bodyweight gain was affected by these treatments. 5. Serum total cholesterol (TC), triglyceride (TG), and glucose (G) levels and the development of atherosclerosis were unaffected by either GLA or EPA treatment. 6. In summary, chronic EPA but not GLA treatment slightly reduced BP elevation in SHR. Although chronic GLA or EPA treatment increased the respective serum level, these treatments unaltered serum TC, TG and G levels, and could not prevent the development of aortic atherosclerosis in SHR.

Topics: Animals; Arteriosclerosis; Blood Pressure; Eicosapentaenoic Acid; Erythrocytes; gamma-Linolenic Acid; Hypertension; Lipids; Male; Rats; Rats, Inbred SHR

The effect of dietary supplementation with evening primrose oil (containing 70% gammalinolenic acid) on the concentration of plasma lipids and lipoproteins of the New Zealand White rabbit was investigated. No significant changes were observed in the concentrations of plasma cholesterol or triglycerides during the treatment, although an increase in high density lipoprotein (HDL) cholesterol (P < 0.01) was observed at 4 weeks of evening primrose oil intake and 2 weeks after withdrawal. However, when HDL subpopulations were resolved by gradient gel electrophoresis, major alterations were observed in the distribution of HDL subfractions. These included an increase in HDL2b (P < 0.001) and HDL3c (P < 0.001) and the appearance of very large particles of HDL. These findings suggest that supplementation of diets with n-6 fatty acids may be effective in the long-term prevention of atherosclerosis.

Topics: Animals; Arteriosclerosis; Cholesterol; Cholesterol, HDL; Diet; Fatty Acids, Essential; Female; gamma-Linolenic Acid; Hypercholesterolemia; Linoleic Acids; Linolenic Acids; Lipoproteins, HDL; Lipoproteins, LDL; Oenothera biennis; Plant Oils; Rabbits; Triglycerides

Male rabbits (10 weeks old) were fed, for 20 weeks, purified diets rich in fat (45% of calories) containing saturated fats (butter), polyunsaturated fats (evening primrose oil + butter or sunflower oil + butter) for 20 weeks. Linoleic acid represented respectively 3.6, 33 and 34% of the dietary fatty acids, while gamma-linolenic acid was present (4.4%) solely in the second group. A significant increase in di-homo-gamma-linolenic acid in plasma, platelets and aorta was noted only in the animals fed evening primrose oil. Despite this, the results of the platelet aggregation to thrombin and ADP, the recalcification plasma-clotting time (platelet-rich plasma) and the severity of atherosclerosis were not significantly different from those observed in the group fed sunflower oil. In contrast, in comparison to the butter-fed animals, the two groups fed the polyunsaturated fats showed remarkable improvements in the clotting time (P less than 0.01) and in the severity of atherosclerotic lesions (evening primrose oil P less than 0.001; sunflower oil P less than 0.05). However, the response to thrombin-induced aggregation was significantly decreased (P less than 0.05) only in the evening primrose oil-fed animals. In these long-term studies in young rabbits, dietary gamma-linolenic acid did not seem to have marked beneficial effects, additional to those induced by linoleic acid, on platelet functions or on atherosclerosis.

Topics: Adenosine Diphosphate; Animals; Arteriosclerosis; Blood Platelets; Dietary Fats; Fatty Acids; gamma-Linolenic Acid; Linoleic Acids; Linolenic Acids; Lipids; Platelet Aggregation; Rabbits