ENDOLUMINAL LOCAL-DELIVERY OF PCNA CDC2 ANTISENSE OLIGONUCLEOTIDES BYPOROUS BALLOON CATHETER DOES NOT AFFECT NEOINTIMA FORMATION OR VESSELSIZE IN THE PIG CORONARY-ARTERY MODEL OF POSTANGIOPLASTY RESTENOSIS/

Localized delivery of antisense oligonucleotides directed against cell cycle regulatory proteins has been proposed as a means to prevent res tenosis after angioplasty, To test whether single endoluminal delivery of a combination of proliferating cell nuclear antigen (PCNA) and cel l-division cycle 2 kinase (cdc2) antisense might affect restenosis, we delivered 2 mi of lipid-complexed PCNA/cdc2 antisense oligomers (1,35 mg) to the coronary arteries of pigs after balloon overstretch angiop lasty (AS group) and performed planimetric histomorphometry an arteria l sections of the tissue, harvested at 4 wk, Compared with controls re ceiving 3'-5' reversed sequence oligomers (REV group), there were no d ifferences in absolute intimal area (AS 1.36 +/- 0.08 mm(2), REV 1.23 +/- 0.10 mm(2), 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 sing le endoluminal delivery of antisense against key cell cycle regulatory proteins does not affect neointima formation or vessel size in this m odel of restenosis. (C) 1997 Wiley-Liss, Inc.