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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1994 Jun;93(6):2351–2356. doi: 10.1172/JCI117240

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

M Simons 1, E R Edelman 1, R D Rosenberg 1
PMCID: PMC294440  PMID: 7911126

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.

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Selected References

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