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 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. 2. 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. 3. 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. 4. Immunohistochemistry showed that local delivery of 10(-5) or 10(-4) M cytochalasin D for 2 weeks suppressed collar-induced alpha-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. 5. 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.
Bruijns
R H
RH
Laboratory of Pharmacology, University of Antwerp (UIA), Faculty of Medical and Pharmaceutical Sciences, Universiteitsplein 1, B-2610 Wilrijk, Belgium.
Bult
H
H
D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D015638:Cytochalasin D / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D006965:Hyperplasia; D007260:Infusion Pumps; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects* / Q000473:pathology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000008:administration & dosage*; D009924:Organ Culture Techniques; D011817:Rabbits; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology*; D014661:Vasoconstriction / Q000187:drug effects
D019384:Nucleic Acid Synthesis Inhibitors; D015638:Cytochalasin D