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Western Diet Increases Inflammatory Responses and Atherosclerosis Progression via IGF‐1 Receptor in ApoE‐Deficient Mice
Author(s) -
Wang Meifang,
Higashi Yusuke,
Wang Derek,
Korthuis Ronald,
Delafontaine Patrice
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.729.1
Subject(s) - apolipoprotein e , endocrinology , medicine , monocyte , cytokine , apolipoprotein b , inflammation , tumor necrosis factor alpha , biology , immunology , cholesterol , disease
Atherosclerosis is the principal underlying cause of most cardiovascular disease‐related deaths, the leading cause of mortality in the US. Insulin‐like growth factor‐1 (IGF‐1) is the primary mediator of the effect of growth hormone on developmental growth which is expressed in vascular cells and monocytes/macrophages. But its role in atherosclerosis is unknown. Our previous studies show that lowered circulating IGF‐1 increases atherosclerosis progression in atherosclerosis‐prone apolipoprotein E‐deficient mice (ApoE − / − ) while increased circulating IGF‐1 downregulates vascular pro‐inflammatory cytokine gene expression, reduces systemic and vascular oxidant stress, vascular cytokine expression, and decreases atherosclerosis progression. These findings led us to investigate whether the pro‐inflammatory phenotypes became more noticeable in ApoE − / − mice, in which IGF1R‐expression is deleted selectively in monocytes/macrophage (ApoE − / − LC), and whether consumption of a Western diet would change the interaction between monocytes and endothelium cells in these mice and IGF‐1R ApoE − / − ‐flox mice (ApoE − / − ‐FIR). To test these hypotheses, we compared baseline Monocyte Rolling (MR) and Monocyte Adhesion (MA) in both these mice fed with either normal mouse chow (NC) or Western diet (WD). There was no significant change in the pro‐inflammatory phenotype in mice with deficient IGF1R‐expression on macrophages in ApoE − / − mice. However, ingestion of a Western diet markedly increased MR and MA on ApoE − / − LC animals (ApoE − / − LC WD) compared to ApoE − / − LC NC mice, although there was no significant effect on ApoE − / − ‐FIR mice. These findings indicate that the pro‐inflammatory phenotype that is enhanced by WD in ApoE−/− mice is further enhanced by specific IGF1R deficiency in monocytes/macrophages, and may consequently increase atherosclerosis progression. Support or Funding Information R01‐HL59976, P01‐HL ‐095486 & R01‐AA22108, RO1 HL070241 and HL 080682.