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Updated: Jul 20, 2026
A Rabbit Model of Durable Transgene Expression in Jugular Vein to Common Carotid Artery Interposition Grafts
Published on: September 10, 2018
Inhibition of carotis venous bypass graft disease by intraoperative nucleic acid-based therapy in rabbits
B Kusch1, S Waldhans, A Sattler
1Clinic for Cardiac Surgery, University Hospital Giessen and Marburg, Position Marburg, Marburg, Germany.
Background:
Bypass graft stenosis after venous revascularisation procedures is characterised by massive neointimal and vascular smooth muscle cell proliferation triggered via endothelin-1 synthesis in the vessel wall. Decoy oligodesoxynucleotides (ODN) against the transcription factor activator protein-1 (AP-1) inhibits pre-pro-endothelin-1 expression.
Methods:
In 20 rabbits, an end-to-side jugular vein bypass to the carotid artery was performed: (group A) 8 grafts were treated with consensus AP-1 decoy ODN, (group B) 8 with mutated control ODN and (group C) 4 received no treatment. Explantation, histomorphometric and immunohistochemical evaluation was performed after 28 days.
Results:
Median intimal thickness of groups: (A) 28.3 microm, (B) 48.4 microm, (C) 71.1 microm. The decoy ODN-treated group showed a significant reduction of neointima formation ( P = 0.029) and a downregulation of the endothelin receptor.
Conclusions:
In this model, neointima formation was reduced by local transfection with consensus decoy ODN against AP-1. Endothelin A and B receptor expression is downregulated. Molecular target nucleic acid-based therapies seem to be a future means of overcoming neointima proliferation in pressure-induced venous graft failure. Intraoperative local application makes it easy to use in routine revascularisation procedures.
Insights
Decoy oligodeoxynucleotides (ODN) targeting activator protein-1 (AP-1) significantly reduced neointima formation in a rabbit bypass graft model. This nucleic acid therapy shows promise for preventing venous graft failure by inhibiting cell proliferation.
Area of Science:
- Vascular Biology
- Molecular Medicine
- Surgical Research
Background:
- Bypass graft stenosis involves neointimal and smooth muscle cell proliferation.
- Endothelin-1 synthesis in the vessel wall triggers this proliferation.
- Decoy oligodeoxynucleotides (ODN) against activator protein-1 (AP-1) inhibit endothelin-1 expression.
Purpose of the Study:
- To evaluate the efficacy of AP-1 decoy ODN in preventing neointima formation.
- To assess the impact of AP-1 decoy ODN on endothelin receptor expression.
Main Methods:
- An end-to-side jugular vein bypass to the carotid artery was performed in 20 rabbits.
- Grafts were treated with consensus AP-1 decoy ODN, mutated control ODN, or no treatment.
- Histomorphometric and immunohistochemical evaluations were conducted after 28 days.
Main Results:
- The AP-1 decoy ODN group showed significantly reduced intimal thickness (28.3 microm) compared to control groups.
- Neointima formation was significantly reduced (P = 0.029) in the decoy ODN-treated group.
- Downregulation of the endothelin receptor was observed in the decoy ODN group.
Conclusions:
- Local transfection with AP-1 decoy ODN effectively reduced neointima formation in this model.
- Endothelin A and B receptor expression was downregulated.
- Nucleic acid-based therapies offer a future strategy for preventing venous graft failure, with easy intraoperative application.
