Insulin-like growth factor-1 stimulates vascular smooth muscle cell proliferation in rat aorta in vivo

IGF-I is a mitogen for vascular smooth muscle cells (SMC) in vitro and enhances SMC proliferation in vivo in diabetic rats. In this study, we examined the effect of IGF-I on SMC proliferation in vivo in normal rats. Recombinant human IGF-I (0.87 and 3.1 mg/kg/day), was infused via osmotic minipumps in normal rats starting 3 days before they were subjected to aortic injury with a balloon catheter. IGF-I at an infusion rate of 3.1 mg/kg/day caused a significant increase in 3H-thymidine incorporation into DNA (+53%, P < 0.01) in the rat aortic intima-media 2 days after injury and DNA content (+13%, P < 0.05) after 11 days. The elastin and collagen contents were not changed by IGF-I infusion after 11 days. Body weight increased slightly while blood glucose was not affected. At an infusion rate of 0.87 mg/kg/day, IGF-I had no significant effects. These results suggest that circulating levels of IGF-I can stimulate SMC proliferation in vivo in normal rats but only at high concentrations.