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Arterial injury in mice with severe insulin-like growth factor-1 (IGF-1) deficiency.

Authors: Li, H  Dimayuga, P  Yamashita, M  Yano, J  Fournier, M  Lewis, M  Cercek, B 
Citation: Li H, etal., J Cardiovasc Pharmacol Ther. 2002 Oct;7(4):227-33.
Pubmed: (View Article at PubMed) PMID:12490968

BACKGROUND: Insulin-like growth factor-1 plays a significant role in wound healing. Injury to the arterial wall is followed by a marked increase in insulin-like growth factor-1 expression and inhibition of insulin-like growth factor-1 action is associated with diminished intimal thickening after injury. METHODS AND RESULTS: The role of insulin-like growth factor-1 in arterial response to cuff injury was investigated in genetically modified mice with severe insulin-like growth factor-1 deficiency ((m/m) mice). Tissue and serum insulin-like growth factor-1 was severely decreased, by 40% to 60% before the injury and by 50% to 60% following the arterial injury in insulin-like growth factor-1 (m/m) mice compared to control mice. Nevertheless, following the cuff induced injury to the carotid arteries, insulin-like growth factor-1 (m/m) mice had a similar number of proliferating medial cells 3 days after injury and similar neointimal thickening (0.019 +/- 0.015 C57BL/6J vs. 0.016 +/- 0.014 mm(2), P = 0.26) 21 days after injury compared to wild type C57BL/6J mice. The phases of the response to injury that are mediated by insulin-like growth factor-1 were studied with recombinant human insulin-like growth factor-1 in rats with balloon-injured femoral arteries. Treatment of rats with recombinant human insulin-like growth factor-1 increased neointimal thickening (0.0265 +/- 0.0099 vs 0.0156 +/- 0.0049 mm(2), P = 0.03), intimal smooth muscle cell numbers (195.6 +/- 40.2 vs 145.3 +/- 27.3; P = 0.03), and the ratio of proliferating intimal to medial smooth muscle cells (10.7 +/- 6.9 vs 3.0 +/- 2.1; P = 0.03) 7 days after injury compared to untreated rats. At 14 days neointimal area was similar in the 2 groups of rats. CONCLUSIONS: The data in insulin-like growth factor-1 deficient mice suggest a relatively low threshold tissue concentration for insulin-like growth factor-1 to exhibit its role in vascular response to injury. The findings in rats treated with recombinant human insulin-like growth factor-1 suggest that insulin-like growth factor-1 is primarily involved in the early phases of neointimal formation.

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CRRD Object Information
CRRD ID: 10046051
Created: 2015-07-02
Species: All species
Last Modified: 2015-07-02
Status: ACTIVE



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