Effect of dietary omega-3 fatty acid on serum lipids, platelet function, and atherosclerosis in Watanabe heritable hyperlipidemic rabbits.

Abstract

Omega-3 fatty acids have been shown to lower plasma cholesterol and triglycerlde concentrations In humans. However, the effects of these fatty acids on the Interactions among llpld concentrations, platelet activity, and atherogenesls have not been characterized In humans or In animals with low density llpoproteln (LDL) receptor deficiencies. To test the hypothesis that omega-3 fatty adds exert a protective effect In LDL receptor-deficient animals by lowering hyperlipldemla, reducing platelet aggregation, and reducing the severity of atherosclerosis, we evaluated young homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits that were fed omega-3 fatty adds. One-month-old male and female WHHL rabbits were placed on either a control diet (standard laboratory rabbit chow) or a diet supplemented with Menhaden fish oil (MFO), which contained elcosapentaenolc acid (EPA). Consumption measurements during the 5 months of the study Indicated that the MFO-fed group received 150 to 200 mg/kg/day of EPA. Six-month-old, MFO-fed, female WHHL rabbits had significantly lower plasma concentrations of total cholesterol (582±20 mg/dl vs. 856±44 mg/dl, control, p<0.05) and triglycertdes (266±21 mg/dl vs. 459±15 mg/dl, control, p<0.05), with lower serum/plasma llpoproteln concentrations [very low density llpoproteln (VLDL), LDL, high density llpoproteln (HDL)] compared to control female WHHL rabbits. Male MFO-fed rabbits had only significantly lower VLDLs (46±9 mg/dl) compared to control male WHHL rabbits (156±9 mg/dl, p<0.05). The platelet fatty acid composition In MFO-fed rabbits had significantly greater amounts of omega-3 fatty adds and lesser amounts of omega-6 fatty acids. Additionally, the threshold concentration of collagen and arachldonate required to aggregate platelets In MFO-fed rabbits was nearly double that of controls. In contrast, the platelet aggregation response to the thromboxane analogue, U-46619, was similar in both groups of animals. Morphometric evaluation of intimal surface of the aortas failed to demonstrate significant differences In llpld accumulation or Intimal or medial thickening between MFO-fed and control WHHL rabbits, even when the potential effects of gender were considered. In conclusion: 1) omega-3 fatty adds exert hypdlpldemlc and antlplatelet effects In LDL receptor-defldent animals, and 2) despite these actions, omega-3 fatty adds do not reduce the severity of atherosclerosis In WHHL rabbits. (Arteriosclerosis 9:529-537, July/August 1989)

Fish oil and the prevention and regression of atherosclerosis

“…Animal studies with hypercholesterolemia Tables 2-4 list the in vivo studies in rabbits [58][59][60][61][62][63][64][65][66][67][68][69], swine [23,28,[70][71][72][73] and monkeys [74][75][76], respectively, on the effects of fish oil on the prevention of atherosclerosis and provides details such as the dietary regimen, duration of study, etc. Except in the Watanabe hereditary hyperlipidemic rabbit and one study in pigs [73], all atherogenic diets are highcholesterol diets, and in case of the swine model [28,[70][71][72], bile acids were also needed to enhance hypercholesterolemia.…”

“…In all studies the number of anireals used is comparable (from five to twelve). After judging the results of the twelve rabbit studies and classifying them very globally one can conclude that an equal number of studies report a favorable [60,64,66,67], unfavorable [58,62,65,68] or no effect [59,61,63,69). For the swine studies four [23,[71][72][73] are favorable and two [28,70] show no effect, while in the non-human primates two [74,75] are beneficial and one study [76] shows no effect at all.…”

Seminars in Thrombosis, Thrombolysis and Vascular Biology

“…The n-3 class of polyunsaturated fatty acids, particularly eicosapentaenoic acid, may be valuable in preventing the thrombotic complications of cardiovascular disease [16], Omega-3 fatty acid supplementation decreases the platelet membrane concentration of arachidonic acid, preventing thromboxane A2 synthesis. In addition, eicosapentaeonic and docosahexaenoic acids compete with arachidonic acid for cyclo-oxygenase, leading to the for mation of three biologically inactive prosta noids -PGG3.…”

Radical Scavenging and Inhibition of Platelet Function by a Polyphenol-Rich Fraction from Salvia miltiorrhiza Bunge

“…Given the importance of thrombosis in cardiovascular disorders, natural products, for example, extracts from Ginkgo biloba [4], garlic [5], and onion [6], as well as omega-3 fatty acids from fish oil [7], have been screened for anti-platelet activity. Likewise, flavonoid-rich foods such as grapes juice [8] and cocoa [9], as well as catechin, epicatechin, and procyanidine have been shown to modify platelet function [10].…”