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Enhanced Aortic Macrophage Lipid Accumulation and Inflammatory Response in LDL Receptor Null Mice Fed an Atherogenic Diet

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Lipids

Abstract

The effect of an atherogenic diet on inflammatory response and elicited peritoneal macrophage (Mϕ) cholesterol accumulation in relation to aortic lesion formation was assessed in LDL receptor null (LDLr−/−) mice. Mice were fed an atherogenic or control diet for 32 weeks. The atherogenic relative to control diet resulted in significantly higher plasma monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) concentrations, more aortic wall Mϕ deposition, higher serum non HDL-cholesterol concentrations and total cholesterol to HDL-cholesterol ratios, and greater accumulation of both aortic free and esterified cholesterol. Elicited peritoneal Mϕ selectively accumulated longer chain unsaturated fatty acids in their membrane, independent of the dietary fatty acid profile. Elicited peritoneal Mϕ isolated from mice fed the atherogenic relative to control diet had significantly less arachidonic acid levels, accumulated significantly higher esterified cholesterol, had significantly higher mRNA levels and secretion of MCP-1, and mRNA and protein levels of ATP-binding cassette A1. Diet treatment had no significant effect in elicited peritoneal Mϕ on TNFα and IL-6 mRNA levels and secretion. These data suggest that the atherogenic relative to control diet resulted in higher plasma inflammatory factor concentrations, less favorable lipoprotein profile, higher elicited peritoneal Mϕ cholesterol accumulation and inflammatory factor secretion, and more aortic wall Mϕ deposition, which in turn were associated with greater aortic cholesterol accumulation.

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Abbreviations

Mϕ:

Macrophage

LDLr−/−:

LDL receptor null

MCP-1:

Monocyte chemoattractant protein-1

TNFα:

Tumor necrosis factor alpha

IL-6:

Interleukin-6

MSR1:

Membrane bound Mϕ scavenger receptor 1

CD36:

Cluster of differentiation 36

ABCA1:

ATP-binding cassette A1

SR-B1:

Scavenger receptor B class 1

CCR2:

CC chemokine receptor 2

PBS:

Phosphate-buffered saline

TC:

Total cholesterol

FC:

Free cholesterol

EC:

Esterified cholesterol

BCA:

Bicinchoninic acid

HDL-C:

High density lipoprotein-cholesterol

non HDL-C:

Non-high density lipoprotein-cholesterol

LPS:

Lipopolysaccharide

SD:

Standard deviation

MUFA:

Monounsaturated fatty acid

PUFA:

Polyunsaturated fatty acid

ALA:

Alpha-linolenic acid

EPA:

Eicosapentaenoic acid

DHA:

Docosahexaenoic acid

LNA:

Linoleic acid

ARA:

Arachidonic acid

CVD:

Cardiovascular disease

TLR4:

Toll-like receptor 4

NF-kB:

Nuclear factor-kappa B

ox-LDL:

Oxidized LDL

LXR:

Liver-X-receptors

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Acknowledgments

The authors are grateful for the technical expertise provided by Susan Jalbert, and Drs. Donald Smith and Mohsen Meydani, and for the thoughtful manuscript review by Drs. Julian Marsh and Alice Dillard. This project was supported by T32 HL69772-01A1 (S.W., J.L.), RO1 HL 54727 and USDA agreement 588-1950-9-001. Any opinions, findings, conclusions or recommendations expressed in this publication are those of authors, and do not necessarily reflect the view of USDA.

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All authors have no conflict of interest.

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Author notes

  1. Shu Wang

    Present address: Department of Nutrition, Hospitality and Retailing, Texas Tech University, Lubbock, TX, 79409, USA

Authors and Affiliations

  1. Cardiovascular Nutrition Laboratory, JM USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA, 02111, USA

    Shu Wang, Nirupa R. Matthan, Jaime L. Lecker & Alice H. Lichtenstein

  2. Nutritional Immunology Laboratory, JM USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA, 02111, USA

    Dayong Wu

  3. Lipid Metabolism Laboratory, JM USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA, 02111, USA

    Stefania Lamon-Fava

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  1. Shu Wang
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  4. Stefania Lamon-Fava
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Correspondence to Alice H. Lichtenstein.

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Wang, S., Wu, D., Matthan, N.R. et al. Enhanced Aortic Macrophage Lipid Accumulation and Inflammatory Response in LDL Receptor Null Mice Fed an Atherogenic Diet. Lipids 45, 701–711 (2010). https://doi.org/10.1007/s11745-010-3454-8

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