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Updated: Aug 8, 2026
A Murine Model of Stent Implantation in the Carotid Artery for the Study of Restenosis
Published on: May 14, 2013
Chimeric DNA-RNA hammerhead ribozyme to proliferating cell nuclear antigen reduces stent-induced stenosis in a
A Frimerman1, P J Welch, X Jin
1Cardiovascular Intervention Center, Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, USA.
Background:
Stent-induced coronary restenosis is a major clinical and public health problem. Proliferating cell nuclear antigen (PCNA) is an important regulator of cell division, and blocking of its expression after angioplasty may limit intimal proliferation.
Methods And Results:
We cloned the porcine PCNA gene and constructed a chimeric hammerhead ribozyme to a segment of the gene with human homology. In vitro studies with both cultured porcine and human vascular smooth muscle cells demonstrated uptake of ribozyme within the nucleus and significant inhibition of cellular proliferation. The ribozyme was then delivered locally into pig coronaries in a stent model. At 30 days, histomorphometric analysis showed neointimal thickness of 0.51+/-0.20 mm in the ribozyme group versus 0.71+/-0.27 and 0.66+/-0.25 mm in stent controls and scrambled ribozyme control, respectively (P=0.002, P=0.03). Quantitative angiographic analysis showed late loss of 1.4+/-0.5 mm for ribozyme versus 1.9+/-0.4 and 2.0+/-0.4 mm for the controls (P=0.05 and P=0. 02).
Conclusions:
Chimeric hammerhead ribozyme to PCNA inhibits smooth muscle cell proliferation in vitro and reduces both histomorphometric and angiographic restenosis in the porcine coronary stent model when delivered locally.
Insights
A novel ribozyme targeting proliferating cell nuclear antigen (PCNA) effectively inhibited smooth muscle cell proliferation. This approach reduced restenosis in a porcine coronary stent model, offering a potential new therapy.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Biotechnology
Background:
- Stent-induced coronary restenosis is a significant clinical challenge.
- Proliferating cell nuclear antigen (PCNA) regulates cell division and is a target for limiting intimal hyperplasia.
Purpose of the Study:
- To develop and evaluate a chimeric hammerhead ribozyme targeting PCNA for the prevention of restenosis.
- To assess the efficacy of PCNA-targeted ribozyme in inhibiting vascular smooth muscle cell proliferation and reducing neointimal hyperplasia in a porcine coronary stent model.
Main Methods:
- Cloning of the porcine PCNA gene and construction of a chimeric hammerhead ribozyme.
- In vitro studies using cultured porcine and human vascular smooth muscle cells to assess ribozyme uptake and antiproliferative effects.
- Local delivery of the ribozyme into porcine coronary arteries within a stent model, followed by histomorphometric and angiographic analysis at 30 days.
Main Results:
- In vitro studies demonstrated significant inhibition of vascular smooth muscle cell proliferation.
- Histomorphometric analysis revealed reduced neointimal thickness in the ribozyme group compared to controls (0.51 mm vs. 0.71 mm and 0.66 mm, P=0.002).
- Quantitative angiographic analysis showed a significant reduction in late lumen loss in the ribozyme-treated group (1.4 mm vs. 1.9 mm and 2.0 mm, P=0.05).
Conclusions:
- A chimeric hammerhead ribozyme targeting PCNA effectively inhibits smooth muscle cell proliferation in vitro.
- Local delivery of the PCNA-targeted ribozyme significantly reduces both histomorphometric and angiographic measures of restenosis in a porcine coronary stent model.
