TY - JOUR
T1 - Enhanced aortic macrophage lipid accumulation and inflammatory response in KDI receptor null mice fed an atherogenic diet
AU - Wang, Shu
AU - Wu, Dayong
AU - Matthan, Nirupa R.
AU - Lamon-Fava, Stefania
AU - Lecker, Jaime L.
AU - Lichtenstein, Alice H.
N1 - Funding Information:
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.
PY - 2010/8
Y1 - 2010/8
N2 - 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 arachi-donic 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.
AB - 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 arachi-donic 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.
KW - Atherogenic diet
KW - Atherosclerosis
KW - Cholesterol accumulation
KW - Inflammatory response Macrophage
KW - LDLr-/-mouse
UR - http://www.scopus.com/inward/record.url?scp=77957868100&partnerID=8YFLogxK
U2 - 10.1007/s11745-010-3454-8
DO - 10.1007/s11745-010-3454-8
M3 - Article
C2 - 20686867
AN - SCOPUS:77957868100
SN - 0024-4201
VL - 45
SP - 701
EP - 711
JO - Lipids
JF - Lipids
IS - 8
ER -