Effects of local cytochalasin D delivery on smooth muscle cell migration and on collar-induced intimal hyperplasia in the rabbit carotid artery

1 Smooth muscle cell (SMC) migration has been implicated in neointima forma tion after angioplasty. Therefore, we investigated whether cytochalasin D, a fungal metabolite that inhibits. actin filament formation, suppressed SMC migration and collar-induced intimal hyperplasia in the rabbit carotid art ery. 2 To establish effective concentrations, contractions of carotid artery rin gs to phenylephrine were determined after incubation with cytochalasin D (1 0(-8)-10(-6) M) for 30 min or 3 days. In vitro cell migration was studied u sing carotid artery explants and a modified Boyden chamber with SMCs isolat ed from the rabbit aorta. The in vivo effect was tested after infusion of 1 0(-8)-10(-4) M cytochalasin D into collars placed around the left carotid a rtery; collars placed around the right artery served as controls. 3 Contractions to phenylephrine decreased after 30 min or 3 days exposure t o 10(-7) and 10(-6) M cytochalasin D; the effect was partly reversible. The se concentrations also inhibited cellular outgrowth and SMC migration in th e in vitro assays. 4 Immunohistochemistry showed that local delivery of 10(-5) or 10(-4) M cyt ochalasin D for 2 weeks suppressed collar-induced a-SMC actin expression in the intima by 68% and 84% respectively. However, the cross-sectional area of the intima was not reduced due to an influx of T-lymphocytes and macroph ages. 5 It is concluded that cytochalasin D suppressed SMC contractility and migr ation in vitro. Although perivascular infusion of cytochalasin D inhibited collar-induced SMC migration from media to intima in vivo as well, the inti mal hyperplasia was not reduced due to concomitant development of an inflam matory response.