Inhibition of smooth muscle cell proliferation and migration in vitro by antisense oligonucleotide to c-myb

Purpose: 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 μM 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 μM antisense oligonucleotide, aortic and graft SMC proliferation rates were 32% ± 20% and 56% ± 9% of control samples, respectively. At 25 μM 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.