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Antisense proliferating cell nuclear antigen oligonucleotides inhibit intimal hyperplasia in a rat carotid artery injury model.
M Simons, … , E R Edelman, R D Rosenberg
M Simons, … , E R Edelman, R D Rosenberg
Published June 1, 1994
Citation Information: J Clin Invest. 1994;93(6):2351-2356. https://doi.org/10.1172/JCI117240.
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Research Article

Antisense proliferating cell nuclear antigen oligonucleotides inhibit intimal hyperplasia in a rat carotid artery injury model.

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Abstract

We have used antisense phosphorothioate oligonucleotides to define the role played by proliferating cell nuclear antigen (PCNA) in neointimal accumulation of smooth muscle cells in a rat carotid artery injury model. The short-term extraluminal delivery of 250 nmol of antisense oligonucleotides, but not control oligonucleotides, immediately after arterial injury produces a 77% suppression of PCNA mRNA after 24 h and a 52% decrease in the frequency of medial smooth muscle cells expressing PCNA after 72 h. This reduction in PCNA expression is accompanied by a 59% decrease in the frequency of proliferating medial smooth muscle cells at 3 d as measured by BudR staining and an 80% decrease in neointimal accumulation assessed morphometrically at 2 wk. Thus, the expression of PCNA is required for medial smooth muscle cell growth in vivo and for neointimal formation after arterial injury.

Authors

M Simons, E R Edelman, R D Rosenberg

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