Antisense oligonucleotide to c-myb induces apoptosis in vascular smooth muscle cells in vitro and in vivo

Introduction: Local delivery of antisense oligonucleotide (AS-ODN) to c-myb, decreases neointima formation in a number of animal models, apparently via supression of VSMC proliferation and migration. However, c-Myb may also supress apoptosis in some cell types. We therefore hypothesized that reduction of c-Myb expression using AS-ODN c-myb may induce VSMC apoptosis. Methods: in vitro: porcine VSMC were treated with; vehicle alone, 5μM AS-ODN c-myb or 5μM Sense (SN-) ODN. Apoptosis over 24hrs was determined using; (1) a cell death ELISA, (2) Time lapse video microscopy. In vivo: Pigs underwent a standard PTCA followed by local delivery of 2ml of saline containing 500μg AS-ODN, control arteries were PTCA alone and PTCA + saline delivery. At 6hrs, artery segments of maximal injury were stained by TUNEL and % apoptosis determined. Results: in vitro: (1) AS-ODN treatment increased cell death 2.7 fold (p