Article Text

  1. Y. Higashi1,
  2. S. Sukhanov1,
  3. S.-Y. Shai1,
  4. J. Titterington1,
  5. P. Delafontaine1
  1. 1Section of Cardiology, Tulane University School of Medicine, New Orleans, LA.


Insulin-like growth factor 1 (IGF-1) is an important endocrine and autocrine/paracrine factor that produces a wide range of biologic effects via activation of IGF-1 receptor (IGF-1R). Recently, we reported that continuous IGF-1 infusion suppresses development of atherosclerotic plaques in relatively young (3 months old) apolipoprotein E-deficient mice (apoe null mice) fed a cholesterol-rich diet, presumably by decreasing inflammatory responses. To examine whether IGF-1 administration prevents preexisting atherosclerotic plaque progression, we infused 7-month-old apoe null mice with 1.5 mg/kg/d IGF-1 or saline for 8 weeks using osmotic minipumps and evaluated changes in atherosclerotic burden. In saline-infused control animals, atherosclerotic lesion size in the aortic sinus root was increased by 30% (baseline; 439 ± 59 × 1,000 μm2 vs saline infusion; 573 ± 41 × 1,000 μm2, n = 6, p < .05), showing time-dependent progression of atherosclerosis. In marked contrast, there was no increase in lesion size in IGF-1-infused apoe null mice (baseline; 439 ± 59 × 1,000 μm2 vs IGF infusion; 419 ± 37 × 1,000 μm2, n = 6, p = .38), indicating IGF-1 prevented progression of preexisting atherosclerotic lesions. To determine mechanisms, we overexpressed IGF-1R using recombinant adenovirus in cultured macrophages (MΦ) exposed to 100 μg/mL native LDL (nLDL) or oxidized LDL (oxLDL) for 24 hours. IGF-1R up-regulation markedly inhibited MΦ lipid accumulation and foam cell formation (85 ± 11% inhibition vs MΦ infected with GFP adenovirus, n = 4, p < .05). Furthermore, flow cytometry analysis indicated that IGF-1 infusion increased levels of circulating Sca-1/Flk-1 positive endothelial progenitor cells (EPCs), which are thought to contribute to endothelial repair (3.46 ± 2.1% in IGF-1-infused mice vs 0.96 ± 0.28% in saline-infused mice, n = 6). In conclusion, our data demonstrate that IGF-1 markedly suppresses atherosclerotic plaque progression in apoe null mice, potentially via prevention of foam cell formation and lipid accumulation in lesions and via promotion of endothelial repair by increasing circulating EPCs. Our findings establish a new paradigm for IGF-1 effects on the cardiovascular system.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.