title: Inhibition of smooth muscle cell proliferation and migration in vitro by antisense oligonucleotide to c-myb.
abstract: OBJECTIVE
  Smooth muscle cell (SMC) migration and proliferation are prominent features of intimal hyperplasia. Previous studies have shown that inhibition of c-myb inhibits arterial SMC proliferation. Our goal was to evaluate the effect of an antisense oligonucleotide targeted to c-myb on the proliferation and migration of SMC explanted from synthetic vascular grafts.
  
  
  METHODS
  SMCs were enzymatically removed from aortas and Dacron grafts explanted from dogs (n = 5). For proliferation studies, quiescent SMCs were incubated with either 0.0, 0.5, 5.0, or 10.0 microM antisense (GTGTCGGGGTCTCCGGGC) or sense (GCCCGGAGACCCCGACAC) oligonucleotides to c-myb. Proliferation was measured after 24 hours by incorporation of [3H]thymidine. Migration was assessed 24 hours after a razor injury.
  
  
  RESULTS
  Antisense to c-myb consistently inhibited proliferation and migration of both native aortic and graft SMCs in a dose-dependent fashion. At a concentration of 10 microM antisense oligonucleotide, aortic and graft SMC proliferation rates were 32% +/- 20% and 56% +/- 9% of control samples, respectively. At 25 microM antisense, the number of migrating aortic and graft SMCs decreased to 41.9% +/- 26.8% and 51.9% +/- 34.1% of control samples, respectively.
  
  
  CONCLUSIONS
  Our results suggest that antisense oligonucleotides to c-myb may be useful in the inhibition of SMC proliferation and migration associated with development of intimal hyperplasia.
authors.affiliation: Department of Surgery, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Pitsch
authors.forename: G R
authors.initials: GR
authors.lastname: Goodman
authors.forename: D J
authors.initials: DJ
authors.lastname: Minion
authors.forename: J A
authors.initials: JA
authors.lastname: Madura
authors.forename: P L
authors.initials: PL
authors.lastname: Fox
authors.forename: L M
authors.initials: LM
authors.lastname: Graham
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D001483:Base Sequence; D001807:Blood Vessel Prosthesis; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006083:Graft Occlusion, Vascular / Q000517:prevention & control; D006965:Hyperplasia / Q000517:prevention & control; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D009857:Oncogenes; D011093:Polyethylene Terephthalates
chemical_list: D016376:Oligonucleotides, Antisense; D011093:Polyethylene Terephthalates