title: Modulation of macrophage fatty acid content and composition by exposure to dyslipidemic serum in vitro.
abstract: Macrophages in arterial walls accumulate lipids leading to the development of atherosclerotic plaques. However, mechanisms underlying macrophage lipid accumulation and foam cell formation are often studied without accounting for risk factors such as dyslipidemia. We investigated the effect of varying concentrations of triglyceride (TG) within physiological range on macrophage fatty acid (FA) accumulation and expression of cholesterol efflux proteins. Human monocytes were cultured in media supplemented with 10% sera containing low (0.7 mmol/L) to high (1.4 mmol/L) TG. The resulting macrophages were harvested after 10 days for analysis of FA content and composition and expression of genes involved in lipid metabolism. Exposure to higher TG and lower HDL concentrations in media increased macrophage lipid content. Macrophages exposed to higher TG had increased total FA content compared with controls (876 μg/mg protein vs. 652 μg/mg protein) and greater proportions of C16:0, C18:1 and C18:2. Macrophage expression of both ABCA1 and ABCG1 cholesterol efflux proteins were reduced when higher TG concentrations were present in the media. Expression of scavenger receptor CD36, involved in lipoprotein uptake, was also downregulated in macrophages exposed to higher TG. Culturing macrophages in conditions of higher versus lower TG influenced macrophage FA content and composition, and levels of regulatory proteins. Replicating in vitro levels of dyslipidemia encountered in vivo may provide an informative model for investigation of atherogenesis.
authors.affiliation: School of Medicine and Pharmacology, Fremantle and Royal Perth Hospitals, University of Western Australia, Perth, WA, Australia.
authors.forename: Bruce X W
authors.initials: BX
authors.lastname: Wong
authors.forename: Reece A
authors.initials: RA
authors.lastname: Kyle
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Croft
authors.forename: Carmel M
authors.initials: CM
authors.lastname: Quinn
authors.forename: Wendy
authors.initials: W
authors.lastname: Jessup
authors.forename: Bu B
authors.initials: BB
authors.lastname: Yeap
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D050171:Dyslipidemias / Q000097:blood*; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D044967:Serum / Q000737:chemistry*; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000494:pharmacology
chemical_list: C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D018955:CD36 Antigens; D003470:Culture Media; D005227:Fatty Acids; D014280:Triglycerides; D013230:Stearoyl-CoA Desaturase