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


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.
Li
Hongyan
H
Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Dimayuga
Paul
P
Yamashita
Makoto
M
Yano
Juliana
J
Fournier
Mario
M
Lewis
Michael
M
Cercek
Bojan
B
D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology
D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I