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.
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.
Endocrinology and Metabolism Division, Faculty of Medical Sciences of the University of Sao Paulo, Lipids Laboratory, LIM 10, SP, Brazil.
Roberta M
RM
Machado
Edna R
ER
Nakandakare
Eder C R
EC
Quintao
Patricia M
PM
Cazita
Marcia K
MK
Koike
Valeria S
VS
Nunes
Fabiana D
FD
Ferreira
Milessa S
MS
Afonso
Renata P A
RP
Bombo
Adriana
A
Machado-Lima
Francisco G
FG
Soriano
Sergio
S
Catanozi
Ana Maria
AM
Lottenberg
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000818:Animals; D001011:Aorta / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D003094:Collagen / Q000378:metabolism; D059305:Diet, High-Fat; D004042:Dietary Fats, Unsaturated / Q000378:metabolism / Q000627:therapeutic use; D043371:Fatty Acids, Omega-6 / Q000627:therapeutic use*; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency; D044242:Trans Fatty Acids / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D004042:Dietary Fats, Unsaturated; D043371:Fatty Acids, Omega-6; D015850:Interleukin-6; D011973:Receptors, LDL; D044242:Trans Fatty Acids; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D003094:Collagen; D002784:Cholesterol