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Low Serum Insulin‐Like Growth Factor 1 Potentiates Atherosclerotic Plaque Development in APOE‐/‐ Mice: Potential Mechanism of Accelerated Atherosclerosis in Aging
Author(s) -
Shai ShawYung,
Kelly James,
Higashi Yusuke,
Sukhanov Sergiy,
Delafontaine Patrice
Publication year - 2009
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.23.1_supplement.357.9
Subject(s) - apolipoprotein e , medicine , endocrinology , insulin like growth factor , congenic , apolipoprotein b , growth factor , cholesterol , biology , receptor , disease , biochemistry , gene
Aging is associated with reduced serum insulin‐like growth factor‐1 (IGF‐1) and an increased risk of atherosclerosis, but whether lower IGF‐1 plays a causative role is unknown. To determine the relation between serum IGF‐1 levels and atherosclerotic burden independent of age, a congenic mouse strain with 20% reduction in IGF‐1 (C3H.B6‐6T [6T]) was bred into the ApoE ‐/‐ background to obtain C3H.6T +/+/ ApoE ‐/‐ (6T/E) mice to mimic the clinical state of low IGF‐1. Serum IGF‐1 levels in 6T/E mice were similar to those of 6T (6T/E: 208.81 + 58.33 ng/ml vs 6T: 221.41 + 58.33 ng/ml, p=0.6); but lower than those of ApoE ‐/‐ (354.49 + 76.33 ng/ml, p<0.01). 8‐wk old 6T/E, 6T and ApoE ‐/‐ mice were fed normal chow (NC) or western diet (WD) for 12 wks and aortic plaque burden quantified. Plaque area was higher in 6T/E mice than ApoE ‐/‐ whether on NC or WD (% total plaque/aorta, 6T/E, NC: 7.54 + 2.21, ApoE ‐/‐, NC: 4.91 + 3.18, p<0.018; 6T/E, WD: 14.87 + 8.81, ApoE ‐/‐, WD: 8.71 + 3.13, p=0.0005). Body weight gain and blood pressure in 6T/E and ApoE ‐/‐ mice were the same. Thus, in this novel mouse model that mimics age‐related low IGF‐1, a decrease in serum IGF‐1 is accompanied by a diet‐independent increase in aortic atherosclerosis. These results are consistent with epidemiological data indicating that lower IGF‐1 levels are associated with an increased risk for ischemic heart disease, and strongly suggest causality. Supported by NIH HL 70241