promega and Arteriosclerosis

We report the use of a non-invasive ultrasound method to visualize and measure changes in serotonin reactivity of the abdominal aorta during the early stages of atherosclerosis development. Studies were performed at 0, 4, 8, and 14 weeks in New Zealand white rabbits fed a diet enriched with 0.5% cholesterol. Change in systolic vessel diameter at each examination was compared with changes in rabbits fed a control diet or rabbits on a diet enriched with cholesterol plus a concentrated marine lipid. After 4 weeks on the diets, the abdominal aortae of rabbit fed the cholesterol-rich diet displayed an enhanced vasoconstriction to serotonin (P less than 0.01). The enhanced vasoconstriction was observed prior to visible morphologic changes, and progressed when restudied at succeeding examinations. Morphologic abnormalities became evident at 8 weeks in cholesterol-fed animals. Dietary supplementation with marine lipid, rich in polyunsaturated fatty acids, diminished the effect of the atherogenic diet on aortic vasoconstriction.

Topics: Animals; Anticholesteremic Agents; Aorta, Abdominal; Aortic Diseases; Arteriosclerosis; Diet, Atherogenic; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Male; Rabbits; Serotonin; Ultrasonography; Vasoconstriction

Twenty-seven New Zealand white rabbits underwent balloon de-endothelialization of the aorta and iliac arteries while consuming a 2% cholesterol, 10% peanut oil rabbit chow. Ten of these rabbits were fed 1 ml of concentrated marine fish lipid (MaxEpaTm) daily. Six weeks after de-endothelialization, angiography of the treated arteries was performed and histologic cross-sections of the terminal aorta were measured with a planimeter. Iliac artery luminal diameters were also measured at consecutive 3-mm divisions from the aortic bifurcation and found to have a mean lumen diameter of 1.60 +/- 0.08 mm in the marine lipid-supplemented group (M) and 1.38 +/- 0.12 mm in the control group (C) (P less than 0.001). Analysis of variance on individual segmental diameters confirmed this difference. However, neither the angiographic diameters nor histologic, cross-sectional, luminal areas of the terminal aorta were different between groups. Instead, the mean cross-sectional area of the terminal aortic wall was significantly greater in the marine lipid-fed group (4.4 +/- 1.2 mm2 in M and 3.1 +/- 0.6 mm2 in C, P less than 0.01). In addition, the vessel wall area showed a positive correlation with red blood cell (RBC) incorporation of docosahexaenoic acid (r = 0.82, P less than 0.005) in both groups. In the M group, RBC eicosapentaenoic acid and docosahexaenoic acids increased 100% and 650%, respectively, over baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Aorta; Arteriosclerosis; Diet, Atherogenic; Disease Models, Animal; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Fish Oils; Rabbits; Radiography

Marine lipids containing omega-3 fatty acids (chiefly, eicosapentanoic acid [EPA] and docosahexanoic acid [DHA]) may inhibit the development of atherosclerotic vascular disease, but the mechanisms responsible for this putative beneficial effect are unknown. We investigated the effects of EPA and DHA in a canine model of accelerated vein graft arteriosclerosis during a 3-month period. Twenty-five dogs were divided into three dietary groups: group I (control), group II (2.5% cholesterol), and group III (2.5% cholesterol plus 2 gm EPA/day [as MaxEPA]). The effects of EPA on vein graft intimal thickening, platelet and vascular prostaglandin metabolism, lipid and lipoprotein receptor metabolism, and hematologic parameters were assessed. Cholesterol feeding caused a significant 54% increase in graft intimal thickness compared with control animals (124.9 +/- 50.4 vs 81.2 +/- 32.4 micron; p = 0.013), which was prevented by supplementation with EPA in group III (56.9 +/- 30.0 micron; p = 0.001 vs group II). Intimal thickness in group III was not significantly different from that of control. EPA supplementation was also associated with a 38% decline in serum thromboxane levels from 457.0 +/- 129.3 pg/0.1 ml in group II to 283.5 +/- 96.9 pg/0.1 ml in group III (p = 0.007). The alterations in lipoprotein metabolism associated with cholesterol feeding were not affected by EPA: in both groups II and III, serum cholesterol and high-density lipoproteins and liver cholesterol content were elevated and hepatic low-density lipoproteins (LDL) receptor content was reduced. There were no differences between the three groups in terms of vein graft or native vessel prostacyclin production, hematocrit, platelet count, or coagulation parameters. In this canine model, dietary supplementation with marine omega-3 fatty acids reduced the extent and magnitude of accelerated vein graft intimal thickening induced by hypercholesterolemia; moreover, this beneficial effect was associated with lower serum thromboxane production and appeared to be independent of alterations in lipoprotein metabolism or LDL receptor density.

Topics: Animals; Arteriosclerosis; Blood Vessel Prosthesis; Cholesterol, Dietary; Docosahexaenoic Acids; Dogs; Drug Combinations; Eicosapentaenoic Acid; Endothelium, Vascular; Fatty Acids, Unsaturated; Female; Fish Oils; Lipoproteins; Liver; Male; Receptors, LDL; Thromboxane A2

Topics: Animals; Arteriosclerosis; Blood Platelets; Cholesterol, Dietary; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Fish Oils; Rabbits; Research Design; Thiobarbiturates

Both random (U.C. Davis) and inbred ("Sea") Japanese quail were fed 8.6% dietary supplements of lard (SF) or fish oil (FO) Maxepa (38% of calories from fat) and 9 months later selected blood vessels were subjected to light and electron microscopy. Serum lipids were measured by means of automatic enzymatic analyses (Beckman Astra and Dupont ACA) following fasting (12-14 h) bleeding times taken at autopsy. VLDL and LDL were determined indirectly. Fatty acid profiles were done on pericardial fat from selected animals. All FO-fed quail averaged 22-48% increase in bleeding time when compared to diet controls or animals fed saturated fat (P less than 0.005). There was a 20% decrease in triacyglycerol (TG) and very low density lipoprotein (VLDL) in the random bred group (P less than 0.01). TG rose in the Sea Quail (NS). Low density lipoprotein (LDL) increased in both random (P less than 0.05) and inbred quail (P less than 0.05), but total cholesterol (TC) significantly increased only in the inbred birds (P less than 0.01). The HDL/LDL ratios in the FO groups were lower than in the controls. SF-fed animals had some fatty streak and/or fatty point formation in their coronary arteries and great vessels. FO-fed birds showed some fat deposits in their coronary arteries and greater accumulation (foam cells) within their great vessels with subendothelial protrusions into the lumen. It is suggested that these latter results may be a response to the relatively higher levels of cholesterol in FO (600 mg/100 g oil) versus SF (95 mg/100 g fat).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arteries; Arteriosclerosis; Bleeding Time; Coturnix; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Fish Oils; Lipids; Male; Microscopy, Electron; Triglycerides

We investigated the influence of fish oil on cholesterol induced atherosclerosis in rabbits. Group I, a control group was fed a cholesterol-free diet, group II was fed a diet supplemented with 1.5% cholesterol, group III received in addition to cholesterol supplementation a purified fish oil concentrate (Maxepa, 2 ml/d). The animals received these diets for 5 months (100 g/d). Aortic atherosclerosis as measured by planimetry of sudanophilic lesions was significantly higher (+59%) in group III as compared with group II, even though serum cholesterol levels were comparable. No differences were found in platelet half-life times between groups II and III, but these values were significantly lower than the half-life of platelets in the control group I. Total serum peroxide levels, expressed as malondialdehyde equivalents were significantly elevated in the fish oil-treated group. This may be due to malondialdehyde modification of the lipoproteins and may be responsible for the enhanced development of atherosclerosis in these animals.

Topics: Animals; Arteriosclerosis; Blood Platelets; Cell Survival; Cholesterol, Dietary; Dietary Fats, Unsaturated; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Female; Fish Oils; Half-Life; Malondialdehyde; Rabbits

Haemodialysis patients have an exceptionally high incidence of death from cardiovascular causes, related in part to abnormalities of lipids and platelets. Eskimos, however, have a low incidence of myocardial infarction and have a high dietary intake of fish, rich in omega-3 polyunsaturated fatty acids. We have, therefore, studied the effect of a fish oil MaxEPA, containing 3.6 g of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid on lipids and platelet function in haemodialysis patients. Following 8 weeks of therapy there was a 35% fall in triglycerides, a 10% rise of high-density lipoprotein (HDL) cholesterol, a 36% rise of HDL2 cholesterol fraction and a 54% rise of the HDL2:HDL3 cholesterol ratio. The platelet aggregation to adenosine diphosphate and collagen was significantly reduced. The activated whole-blood clotting time was prolonged from 141 to 153 s, and 69% of patients showed a reduction of factor VIII related antigen which is usually elevated in haemodialysis patients and is thought to be a marker of endothelial damage. The blood pressure fell from 147/82 to 124/74. We have thus shown that a dietary supplement of eicosapentaenoic acid produces potentially beneficial effects on lipids, platelets, and blood pressure and may help to protect against atheroma and thus cardiovascular mortality in high-risk haemodialysis patients.

Topics: Adolescent; Adult; Arteriosclerosis; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Female; Humans; Lipids; Male; Middle Aged; Platelet Aggregation; Renal Dialysis; Triglycerides