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Updated: Jul 17, 2026
Vascular Balloon Injury and Intraluminal Administration in Rat Carotid Artery
Published on: December 23, 2014
Antisense proliferating cell nuclear antigen oligonucleotides inhibit intimal hyperplasia in a rat carotid artery
M Simons1, E R Edelman, R D Rosenberg
1Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
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.
Insights
Antisense oligonucleotides targeting proliferating cell nuclear antigen (PCNA) significantly reduced smooth muscle cell proliferation and neointimal accumulation in a rat carotid artery injury model. PCNA expression is essential for smooth muscle cell growth and neointimal formation post-injury.
Area of Science:
- Vascular biology
- Cellular and molecular medicine
- Cardiovascular research
Background:
- Vascular injury triggers smooth muscle cell proliferation and migration, leading to neointimal hyperplasia.
- Proliferating cell nuclear antigen (PCNA) is a key marker of cell proliferation and DNA synthesis.
Purpose of the Study:
- To investigate the role of PCNA in smooth muscle cell proliferation and neointimal accumulation following arterial injury.
- To determine if inhibiting PCNA expression can prevent neointimal formation in a rat carotid artery injury model.
Main Methods:
- Antisense phosphorothioate oligonucleotides were used to inhibit PCNA expression in a rat carotid artery injury model.
- PCNA mRNA and protein levels were assessed via RT-PCR and immunohistochemistry.
- Cell proliferation was measured using BrdU incorporation.
- Neointimal area was quantified morphometrically.
Main Results:
- Extraluminal delivery of antisense oligonucleotides targeting PCNA suppressed PCNA mRNA by 77% and protein expression by 52%.
- PCNA inhibition reduced smooth muscle cell proliferation by 59% and neointimal accumulation by 80% at 2 weeks post-injury.
- Control oligonucleotides had no significant effect on PCNA expression or neointimal formation.
Conclusions:
- PCNA expression is critical for medial smooth muscle cell proliferation in vivo.
- Inhibition of PCNA effectively reduces neointimal formation after vascular injury.
- Targeting PCNA represents a potential therapeutic strategy for preventing vascular restenosis.
