Abstract 392: Effects of Dietary Omega-3 Polyunsaturated Fatty Acids Plus Minus Aspirin on Plasma Lipids and Hepatic Gene Expression in ApoE-Deficient Mice
BACKGROUND Omega-3 fatty acids (O3FA) have hypolipemic, anti-inflammatory and atheroprotective effects. Aspirin (ASA) may potentiate these beneficial effects, by altering the production of anti-inflammatory mediators, such as resolvins.
OBJECTIVE To compare the anti-atherogenic effects and gene expression changes of O3FA diet plus minus ASA.
METHODS 12-week old apoE-Ko females were placed for 2 weeks on a O3FA-deficient (O3FA-) diet, and were then treated for 13 weeks with either O3FA-, O3FA+ or O3FA+ASA diet (N=10). RNA from liver (N=4) was isolated and analyzed by Qiagen PCR Array for 84 genes related to cholesterol metabolism. Arteriosclerosis was assessed by en face analysis.
RESULTS O3FA+ diet decreased plasma total cholesterol, triglycerides, phospholipids, free cholesterol and cholesteryl esters between 26%-39% (P<0.0005). Majority of the decrease in cholesterol was due to a lowering of VLDL-C and LDL-C. Similar lipoprotein changes were observed in mice on the O3FA+ASA diet. O3FA+ fed mice showed numerous significant changes in the expression of genes related to cholesterol metabolism. Insig1 was decreased by 1.9-fold, whereas Nr1h4 and Prkaa1 were increased by 1.5 fold. Cholesterol biosynthesis genes, such as Dhcr7, Fdps and Hmgcr were decreased in 1.6, 2, and 1.4-fold, respectively. Expression of Acaa2 and Hmgcs2, genes involved in catabolism of cholesterol, were increased by 1.7-1.8 fold. O3FA+ASA treated mice showed a similar hepatic gene expression profile except PCSK9, which decreased 5.9-fold in these mice but only by 2.5-fold in O3FA+ treated mice. Compared to O3FA- treated control mice, O3FA+ASA treated mice showed 2.2-fold decrease in aortic atherosclerosis, whereas no change compared to control mice was observed with just the O3FA+ diet.
CONCLUSIONS Addition of ASA to the O3FA+ diet showed a greater effect in lowering the expression of PCSK9 in the liver and decreased aortic atherosclerosis. ASA treatment, however, did not show a significant further improvement in the lowering of plasma pro-atherogenic lipoproteins over that observed with the O3FA+ diet, suggesting that the anti-inflammatory property of ASA may account for its anti-atherogenic effect.
- © 2013 by American Heart Association, Inc.