Omega-6 polyunsaturated fatty acids prevent atherosclerosis development in LDLr-KO mice, in spite of displaying a pro-inflammatory profile similar to trans fatty acids

• Published in: Atherosclerosis Vol. 224; no. 1; pp. 66 - 74
• Main Authors: Machado, Roberta M., Nakandakare, Edna R., Quintao, Eder C.R., Cazita, Patricia M., Koike, Marcia K., Nunes, Valeria S., Ferreira, Fabiana D., Afonso, Milessa S., Bombo, Renata P.A., Machado-Lima, Adriana, Soriano, Francisco G., Catanozi, Sergio, Lottenberg, Ana Maria
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.09.2012; Elsevier
• Subjects: ABCA1; Animals; Aorta; Aorta - metabolism; atherogenesis; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Atherosclerosis - metabolism; Atherosclerosis - pathology; Atherosclerosis - prevention & control; ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters; ATP-Binding Cassette Transporters - biosynthesis; Biological and medical sciences; biosynthesis; blood; Blood and lymphatic vessels; blood lipids; Cardiology. Vascular system; Cardiovascular; cholesterol; Cholesterol - blood; collagen; Collagen - metabolism; culture media; deficiency; Diet, High-Fat; Dietary Fats, Unsaturated; Dietary Fats, Unsaturated - metabolism; Dietary Fats, Unsaturated - therapeutic use; energy; Escherichia coli; Fatty acids; Fatty Acids, Omega-6; Fatty Acids, Omega-6 - therapeutic use; high fat diet; immunohistochemistry; Inflammation; Inflammation - metabolism; Inflammation - prevention & control; interleukin-10; Interleukin-10 - metabolism; interleukin-6; Interleukin-6 - metabolism; lipopolysaccharides; macrophages; Macrophages - physiology; Male; Medical sciences; metabolism; Mice; Mice, Knockout; microscopy; oils; omega-6 fatty acids; pathology; pharmacology; physiology; polyunsaturated fatty acids; prevention & control; Receptors, LDL; Receptors, LDL - deficiency; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Saturated fatty acids; therapeutic use; Trans fatty acids; Trans Fatty Acids - pharmacology; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - metabolism; Unsaturated fatty acids; ABCA1; Unsaturated fatty acids; Atherosclerosis; Inflammation; Fatty acids; Saturated fatty acids; Trans fatty acids; Rodentia; Polyunsaturated fatty acid; Lipids; Cardiovascular disease; Vascular disease; Vertebrata; Mammalia; Mouse; Saturated fatty acid; Animal; Unsaturated fatty acid
• ISSN: 0021-9150; 1879-1484; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2012.06.059

The development of atherosclerosis and the inflammatory response were investigated in LDLr-KO mice on three high-fat diets (40% energy as fat) for 16 weeks: trans (TRANS), saturated (SAFA) or ω-6 polyunsaturated (PUFA) fats. The following parameters were measured: plasma lipids, aortic root total cholesterol (TC), lesion area (Oil Red-O), ABCA1 content and macrophage infiltration (immunohistochemistry), collagen content (Picrosirius-red) and co-localization of ABCA1 and macrophage (confocal microscopy) besides the plasma inflammatory markers (IL-6, TNF-α) and the macrophage inflammatory response to lipopolysaccharide from Escherichia coli (LPS). As expected, plasma TC and TG concentrations were lower on the PUFA diet than on TRANS or SAFA diets. Aortic intima macrophage infiltration, ABCA1 content, and lesion area on PUFA group were lower compared to TRANS and SAFA groups. Macrophages and ABCA1 markers did not co-localize in the atherosclerotic plaque, suggesting that different cell types were responsible for the ABCA1 expression in plaques. Compared to PUFA, TRANS and SAFA presented higher collagen content and necrotic cores in atherosclerotic plaques. In the artery wall, TC was lower on PUFA compared to TRANS group; free cholesterol was lower on PUFA compared to TRANS and SAFA; cholesteryl ester concentration did not vary amongst the groups. Plasma TNF-α concentration on PUFA and TRANS-fed mice was higher compared to SAFA. No difference was observed in IL-6 concentration amongst groups. Regarding the macrophage inflammatory response to LPS, TRANS and PUFA presented higher culture medium concentrations of IL-6 and TNF-α as compared to SAFA. The PUFA group showed the lowest amount of the anti-inflammatory marker IL-10 compared to TRANS and SAFA groups. In conclusion, PUFA intake prevented atherogenesis, even in a pro-inflammatory condition. ▸ Omega-6 (PUFA) prevented atherosclerosis even in a pro inflammatory condition. ▸ Trans fatty acids-fed (TRANS) induced hypertriglyceridemia and hypercholesterolemia. ▸ PUFA, TRANS and saturated fatty acids (SAFA) had similar modulation on liver ABCA1 mRNA. ▸ ABCA1 and macrophages did not co-localize in the atherosclerotic lesion.