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

Smooth muscle cell (SMC) migration has been implicated in neointima formation 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 artery. To establish effective concentrations, contractions of carotid artery rings to phenylephrine were determined after incubation with cytochalasin D (10−8 – 10−6 M) for 30 min or 3 days. In vitro cell migration was studied using carotid artery explants and a modified Boyden chamber with SMCs isolated from the rabbit aorta. The in vivo effect was tested after infusion of 10−8 – 10−4 M cytochalasin D into collars placed around the left carotid artery; collars placed around the right artery served as controls. Contractions to phenylephrine decreased after 30 min or 3 days exposure to 10−7 and 10−6 M cytochalasin D; the effect was partly reversible. These concentrations also inhibited cellular outgrowth and SMC migration in the in vitro assays. Immunohistochemistry showed that local delivery of 10−5 or 10−4 M cytochalasin D for 2 weeks suppressed collar-induced α-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 macrophages. It is concluded that cytochalasin D suppressed SMC contractility and migration in vitro. Although perivascular infusion of cytochalasin D inhibited collar-induced SMC migration from media to intima in vivo as well, the intimal hyperplasia was not reduced due to concomitant development of an inflammatory response. British Journal of Pharmacology (2001) 134, 473–483; doi:10.1038/sj.bjp.0704281