Overexpression of p53 increases lumen size and blocks neointima formation in porcine interposition vein grafts

Wan, S., George, S., Nicklin, S., Yim, A. and Baker, A. (2004) Overexpression of p53 increases lumen size and blocks neointima formation in porcine interposition vein grafts. Molecular Therapy, 9(5), pp. 689-698. (doi:10.1016/j.ymthe.2004.02.005)

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Abstract

Patency rates for autologous saphenous vein (SV) conduits used in coronary artery bypass grafts remain poor. Patients with failed grafts are difficult to treat with subsequent interventions, necessitating the development of innovative therapies. Previous studies have suggested that induction of smooth muscle cell (SMC) apoptosis may reduce neointima formation. We overexpressed the proapoptotic gene p53 at the lumenal surface of SV grafts using adenoviral (Ad)-mediated gene transfer in porcine SVs prior to grafting in vivo and analyzed at 7 and 28 days (n = 6 and 7 per group, respectively). p53 overexpression induced a significant upregulation in apoptosis (4 plusminus 0.6% for Adp53-infected grafts vs 0.6 plusminus 0.1% for Adbeta-gal-infected grafts) and reduced neointimal proliferation by 28 plusminus 1% at day 7 postinfection. Adp53-infected grafts had significantly greater lumenal areas than controls at both time points (4.8 plusminus 0.6 mm2 vs 2.9 plusminus 0.5 mm2 and 10.0 plusminus 2.5 mm2 vs 4.2 plusminus 1.2 mm2 at 7 and 28 days, respectively). Total graft areas were also increased at 28 days by p53, indicating positive vessel remodeling. Additionally, the thickening of the neointima was significantly reduced by 68 plusminus 22% and 28 plusminus 3% by p53 overexpression at day 7 and 28, respectively. Importantly, phenotypic changes were maintained at 3 months. Induction of SMC apoptosis by transient p53 overexpression positively influenced vein graft remodeling.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Nicklin, Professor Stuart and Baker, Professor Andrew
Authors: Wan, S., George, S., Nicklin, S., Yim, A., and Baker, A.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Molecular Therapy
Publisher:Nature Publishing Group
ISSN:1525-0016
ISSN (Online):1525-0024

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