Modulation of Macrophage Fatty Acid Content and Composition by Exposure to Dyslipidemic Serum in Vitro

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 varyin...

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Bibliographic Details
Published in:Lipids 2011-04, Vol.46 (4), p.371-380
Main Authors: Wong, Bruce X. W., Kyle, Reece A., Croft, Kevin D., Quinn, Carmel M., Jessup, Wendy, Yeap, Bu B.
Format: Article
Language:English
Subjects:
Atherogenesis
ATP Binding Cassette Transporter 1
ATP Binding Cassette Transporter, Sub-Family G, Member 1
ATP-Binding Cassette Transporters - genetics
ATP-Binding Cassette Transporters - metabolism
Biomedical and Life Sciences
CD36 Antigens - genetics
CD36 Antigens - metabolism
Cells, Cultured
Culture Media - chemistry
Dyslipidemia
Dyslipidemias - blood
Fatty acids
Fatty Acids - chemistry
Fatty Acids - metabolism
Humans
Life Sciences
Lipidology
Macrophage
Macrophages - chemistry
Macrophages - cytology
Macrophages - drug effects
Macrophages - metabolism
Medical Biochemistry
Medicinal Chemistry
Microbial Genetics and Genomics
Neurochemistry
Nutrition
Original Article
Serum - chemistry
Stearoyl-CoA Desaturase - genetics
Stearoyl-CoA Desaturase - metabolism
Triglyceride
Triglycerides - pharmacology
Unsaturated fatty acids
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Summary: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.
ISSN:0024-4201
1558-9307
DOI:10.1007/s11745-011-3528-2