Inhibition of smooth muscle cell proliferation and migration in vitro by antisense oligonucleotide to c-myb.
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.
Pitsch
R J
RJ
Department of Surgery, Case Western Reserve University, Cleveland, OH, USA.
Goodman
G R
GR
Minion
D J
DJ
Madura
J A
JA
Fox
P L
PL
Graham
L M
LM
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
D016376:Oligonucleotides, Antisense; D011093:Polyethylene Terephthalates