Smooth muscle cell (SMC) migration and proliferation has been implicated in the pathogenesis of atherosclerosis and bypass graft stenosis. The c-myb oncogene which regulates SMC growth may play a role in these pathologic conditions. We studied the inhibitory effect on migration of blocking the translation of c-myb with antisense (AS) oligonudeotides (oligos) in an in-vitro injury model. In addition, we attempted to quantify a differential response between SMC's from normal arteries as compared to atherosclerotic arteries. SMC explant cultures were established from a femoral artery of a young trauma victim (normal, n=1) and from atherosclerotic tibial arteries from amputated legs of elderly patients (plaque, n=2). Once confluence had been achieved, SMC's were placed in a quiescent state by incubation with serum deprived medium for 48 hrs. At this time, a linear injury was created and the cells were incubated with serum rich medium (SRM) and seme (S) oligos or AS oligos. After 24 hrs, SMC migration was quantified relative to the line of injury. In the presence of AS oligos, the maximum distance and the number of SMC's migrated were decreased 82% and 84% (p<0.05, ANOVA), respectivety. Further, plaque SMC's tended to migrate further and in greater numbers than normal SMC's. Although a nonspecific inhibitory effect was observed with sense oligos, there was a greater inhibitory effect on migration by AS oligos to c-myb. Therefore, c-myb AS oligos may be useful in treating intimai hyperplastic lesions. Mean Maximum Distance Migrated* Mean Number of Cells Migrated normal plaque normal plaque 8RM 1.8±0.5 2.7±1.0 11±13.9 31.3±8.9 8RM+8 0.9±0.6 0.9±0.4 1.3±1.0 8.3±7.4 8RM+AS 0.3±0.2 0.5±0.2 0.5±0.5 5.5±5.3 Mean ± SD, * mm.
|State||Published - 1997|