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

Abstract

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.

• Authors: R H Bruijns, H Bult
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 134 Issue 3 Pg. 473-83 (Oct 2001) ISSN: 0007-1188 [Print] England
• PMID: 11588101 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nucleic Acid Synthesis Inhibitors
• Cytochalasin D

Topics

• Animals
• Carotid Arteries (drug effects, pathology)
• Cell Division (drug effects)
• Cell Movement (drug effects)
• Cytochalasin D (administration & dosage)
• Dose-Response Relationship, Drug
• Hyperplasia
• Infusion Pumps
• Male
• Muscle, Smooth (drug effects, pathology)
• Nucleic Acid Synthesis Inhibitors (administration & dosage)
• Organ Culture Techniques
• Rabbits
• Tunica Intima (drug effects, pathology)
• Vasoconstriction (drug effects)