title: Locally applied antisense oligonucleotide to proliferating cell nuclear antigen inhibits intimal thickening in experimental vein grafts.
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 microm versus 72 +/- 4 microm; 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 microm 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.
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Fulton
authors.forename: M G
authors.initials: MG
authors.lastname: Davies
authors.forename: L
authors.initials: L
authors.lastname: Barber
authors.forename: E
authors.initials: E
authors.lastname: Svendsen
authors.forename: P O
authors.initials: PO
authors.lastname: Hagen
mesh_terms: D000818:Animals; D005069:Evaluation Studies as Topic; D006965:Hyperplasia; D016376:Oligonucleotides, Antisense; D018809:Proliferating Cell Nuclear Antigen; D011817:Rabbits; D011897:Random Allocation; D017539:Tunica Intima / Q000473:pathology*; D014680:Veins / Q000637:transplantation*
chemical_list: D016376:Oligonucleotides, Antisense; D018809:Proliferating Cell Nuclear Antigen