title: 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.
authors.affiliation: Andreas Gruentzig Cardiovascular Center, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Robinson
authors.forename: N A
authors.initials: NA
authors.lastname: Chronos
authors.forename: E
authors.initials: E
authors.lastname: Schieffer
authors.forename: S J
authors.initials: SJ
authors.lastname: Palmer
authors.forename: G D
authors.initials: GD
authors.lastname: Cipolla
authors.forename: P G
authors.initials: PG
authors.lastname: Milner
authors.forename: S B
authors.initials: SB
authors.lastname: King
mesh_terms: D015906:Angioplasty, Balloon, Coronary / Q000295:instrumentation*; D000818:Animals; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003327:Coronary Disease / Q000473:pathology; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D016503:Drug Delivery Systems / Q000295:instrumentation*; D005260:Female; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D012008:Recurrence; D013552:Swine; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology
chemical_list: D016376:Oligonucleotides, Antisense; D018809:Proliferating Cell Nuclear Antigen; D016203:CDC2 Protein Kinase