Locally applied antisense oligonucleotide to proliferating cell nuclear antigen inhibits intimal thickening in experimental vein grafts

Gregory J. Fulton, Mark G. Davies, Lizzie Barber, Einar Svendsen, Per Otto Hagen

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

This study examines the effect of antisense oligonucleotide to proliferating cell nuclear antigen (PCNA) on the formation of vein graft intimal hyperplasia in vivo, using localized administration. Twenty-four New Zealand white rabbits had a right carotid interposition bypass graft using the external jugular vein and were sacrificed on the 28th postoperative day. To determine the effect of PCNA on the development of intimal hyperplasia, 6 animals had their grafts coated with a pluronic gel containing 18 base antisense oligonucleotide to PCNA (1 mg/ml), 6 received a pluronic gel containing an 18 base nonsense oligonucleotide (1 mg/ml), and 12 animals were controls (6 with and 6 without pluronic gel). These grafts were harvested for morphology and videomorphometry. There was no change in the intimal thickness between the control and gel-treated groups. (70 ± 4 μm versus 72 ± 4 μm; mean ± s.e.m.; p = ns). The presence of nonsense oligonucleotide had no further effect. Antisense PCNA produced a 26% decrease in intimal thickness to 50 ± 4 μm in the treated vein grafts (p < 0.03) without a change in medial thickness. This study shows that a local single application of antisense oligonucleotide to PCNA will reduce the intimal hyperplasia in experimental vein grafts over 28 days.

Original languageEnglish (US)
Pages (from-to)412-417
Number of pages6
JournalAnnals of Vascular Surgery
Volume12
Issue number5
DOIs
StatePublished - Sep 1998
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

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