title: Site-specific influence of polyunsaturated fatty acids on atherosclerosis in immune incompetent LDL receptor deficient mice.
abstract: Polyunsaturated fatty acids (PUFA) are thought to influence plasma lipid levels, atherosclerosis, and the immune system. In this study, we fed male LDL receptor deficient (LDLR(-/-)) mice and immune incompetent LDLR(-/-) RAG2(-/-) mice diets containing predominantly saturated fats (milk fat) or PUFA (safflower oil) to determine if the response to diet was influenced by immune status. Relative to milk fat diet, plasma lipid and VLDL levels in both the LDLR(-/-) and LDLR(-/-) RAG2(-/-) mice fed safflower oil diet were lower, suggesting that the primary effect of PUFA on plasma lipids was not due to its inhibition of the immune system. Neither diet nor immune status influenced hepatic triglyceride production and post-heparin lipase activity, suggesting that the differences in triglyceride levels are due to differences in rates of catabolism of triglyceride-rich lipoproteins. While both diets promoted atherogenesis, both aortic root and innominate artery atherosclerosis in LDLR(-/-) mice was less in safflower oil fed animals. In contrast, a site-specific effect of PUFA was observed in the immune incompetent LDLR(-/-) RAG2(-/-). In these mice, aortic root atherosclerosis, but not innominate artery atherosclerosis, was less in PUFA fed animal. These results suggest that PUFA and the immune system may influence innominate artery atherosclerosis by some overlapping mechanisms.
authors.affiliation: Department of Pathology, University of Chicago, MC 1089, 5841 S. Maryland Avenue, Chicago, IL 60637, USA. reardon@uchicago.edu
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Reardon
authors.forename: Lydia
authors.initials: L
authors.lastname: Blachowicz
authors.forename: Gaorav
authors.initials: G
authors.lastname: Gupta
authors.forename: John
authors.initials: J
authors.lastname: Lukens
authors.forename: Michael
authors.initials: M
authors.lastname: Nissenbaum
authors.forename: Godfrey S
authors.initials: GS
authors.lastname: Getz
mesh_terms: D000818:Animals; D001011:Aorta / Q000276:immunology / Q000473:pathology; D050197:Atherosclerosis / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D015243:Cholesterol, VLDL / Q000097:blood; D004268:DNA-Binding Proteins / Q000235:genetics; D005227:Fatty Acids / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006017:Glycolipids / Q000494:pharmacology; D006023:Glycoproteins / Q000494:pharmacology; D007107:Immune System / Q000187:drug effects* / Q000276:immunology; D016867:Immunocompromised Host; D066292:Lipid Droplets; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011973:Receptors, LDL / Q000235:genetics*; D012450:Safflower Oil / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood
chemical_list: D015243:Cholesterol, VLDL; D004268:DNA-Binding Proteins; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D006017:Glycolipids; D006023:Glycoproteins; C499308:Rag2 protein, mouse; D011973:Receptors, LDL; D014280:Triglycerides; C110367:milk fat globule; D012450:Safflower Oil