Perivascular release of insulin-like growth factor-1 limits neointima formation in the balloon-injured artery by redirecting smooth muscle cell migration

PURPOSE: Insulin-like growth factor-1 (IGF-1) is a potent chemoattractant t o vascular smooth muscle cells (SMCs). The authors hypothesize that perivas cular release of IGF-1 in vivo can direct migration of SMCs away from the l umen and reduce neointima formation in a rabbit model of arterial balloon i njury. MATERIALS AND METHODS: Balloon angioplasty of the common femoral arteries w as performed in adult male New Zealand White rabbits (n = 8 per treatment g roup) and controlled release microspheres delivering either IGF-1 or blank control treatment were implanted perivascularly at the angioplasty site pri or to surgical closure. At 7 days, five arteries per group were harvested a nd cross-sections were subjected to anti-PCNA (proliferating cell nuclear a ntigen) immunostaining to determine the number and distribution of prolifer ating SMCs. At 28 days, the remaining three arteries per group were harvest ed and sections were evaluated for intima-to-media (I/M) ratios by means of VVG-Masson staining. One-way analysis of variance with Fisher protected le ast significant difference post hoc testing was used to determine statistic al significance at P < .05. RESULTS: At 7 days, PCNA(+) medial SMCs assumed a significantly more periph eral (ie, further from lumen) distribution in the vessel wall with use of p erivascular IGF-1 than with use of blank treatment (P < .05). Overall SMC p roliferation was not significantly different, thus the change in distributi on was likely due to directionally altered SMC migration. At 28 days, periv ascular IGF-1 significantly decreased UM ratios by 44% relative to control treatment (P < .05). CONCLUSIONS: Perivascular release of IGF-1 can directionally guide SMC migr ation away from the lumen and reduce neointima in the balloon-injured arter y. This novel strategy might have implications in the development of antire stenosis therapies.