Endoluminal local delivery of PCNA/cdc2 antisense oligonucleotides by porous balloon catheter does not affect neointima formation or vessel size in the pig coronary artery model of postangioplasty restenosis

Abstract

Localized delivery of antisense oligonucleotides directed against cell cycle regulatory proteins has been proposed as a means to prevent restenosis after angioplasty. To test whether single endoluminal delivery of a combination of proliferating cell nuclear antigen (PCNA) and cell-division cycle 2 kinase (cdc2) antisense might affect restenosis, we delivered 2 ml of lipid-complexed PCNA/cdc2 antisense oligomers (1.35 mg) to the coronary arteries of pigs after balloon overstretch angioplasty (AS group) and performed planimetric histomorphometry on arterial sections of the tissue, harvested at 4 wk. Compared with controls receiving 3'-5' reversed sequence oligomers (REV group), there were no differences in absolute intimal area (AS 1.36 +/- 0.08 mm2, REV 1.23 +/- 0.10 mm2, P = NS), intimal area normalized to extent of injury (AS 0.67 +/- 0.03, REV 0.77 +/- 0.10, P = NS), or vessel perimeter (AS 7.72 +/- 0.19 mm, REV 7.36 +/- 0.22 mm, P = NS). We conclude that single endoluminal delivery of antisense against key cell cycle regulatory proteins does not affect neointima formation or vessel size in this model of restenosis.