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Updated: Aug 13, 2026
A Rat Carotid Balloon Injury Model to Test Anti-vascular Remodeling Therapeutics
Published on: September 19, 2016
Surgical injury of rat arteries: genetic control of the remodelling process
G Di Micco1, A Forte, M Cipollaro
1Department of Cardio-Thoracic Sciences, Second University of Naples, via Aquila 144, 80143 Naples, Italy.
Objectives:
Remodelling and restenosis are complex biological processes responsible for bypass and percutaneous transluminal coronary angioplasty failures which are likely to affect many hundreds of genes. We evaluated the effectiveness of topically applied antisense oligonucleotides in reducing the translation of the messenger RNA for the transcription factor c-myc and in reducing stenosis.
Methods:
Surgery was performed under sterile conditions; 60 Wistar-Kyoto male rats were anaesthetized by ketamine. The carotid arteries were isolated through a median incision in the anterior neck region. At the same point, 0.5 mm longitudinal incisions were performed. Haemostasis was obtained by an adventitial 8.0 stitch. Thirty animals were given 150 microg of c-myc antisense oligonucleotide (Group A) while the other 30 animals received 150 microg of c-myc control sense oligonucleotide (Group B). Oligo molecules were locally applied through 100 microl of 20% pluronic gel. Rats were sacrificed at 30 days; carotid arteries were explanted and stained. Qualitative histological analysis was performed in all cases; serial sections were made every 25 micro in seven consecutive rats for each group. Morphometric analysis was also performed, luminal and medial area values recorded and the ratio between the two areas calculated. Data from each animal were compared with the corresponding contralateral carotid artery and expressed as mean+/-standard deviation. Statistical comparison between the two groups was carried out by one-way ANOVA text.
Results:
Qualitative histological analysis showed marked remodelling with complete disarray of vessel wall, neointima accumulation and evidence of elastic fibres in the adventitia of all animals of Group B versus Group A. Morphometric analysis showed a significant reduction in the lumen area in Group A animals together with increased values of the medial area versus Group B animals. In addition, the ratio between the lumen and medial area was significantly higher in Group A than in Group B (2.61+/-0.18 versus 1.14+/-0.33, P<0.0001).
Conclusions:
c-myc antisense oligonucleotides applied intraoperatively can reduce post-operative stenosis.
Insights
Topical c-myc antisense oligonucleotides significantly reduced post-operative stenosis by inhibiting c-myc messenger RNA translation. This targeted approach offers a promising strategy for preventing vascular remodelling and restenosis after surgical procedures.
Area of Science:
- Vascular biology and regenerative medicine.
- Molecular mechanisms of post-surgical complications.
- Gene silencing strategies for cardiovascular disease.
Background:
- Vascular remodelling and restenosis are major causes of bypass and percutaneous transluminal coronary angioplasty failure.
- These processes involve complex genetic pathways, potentially affecting numerous genes.
- Effective therapeutic strategies are needed to mitigate these adverse outcomes.
Purpose of the Study:
- To evaluate the efficacy of topically applied antisense oligonucleotides targeting c-myc messenger RNA (mRNA).
- To assess the impact of c-myc inhibition on reducing stenosis and vascular remodelling.
- To determine the potential of this approach in preventing post-operative vascular complications.
Main Methods:
- A rat carotid artery model was used, with 60 Wistar-Kyoto male rats undergoing surgical procedures.
- Animals received either c-myc antisense oligonucleotide (Group A) or a control sense oligonucleotide (Group B) via topical application in pluronic gel.
- Carotid arteries were analyzed after 30 days using qualitative histological and quantitative morphometric analysis to assess lumen and medial areas.
Main Results:
- Histological analysis revealed marked disarray of the vessel wall and neointima accumulation in control animals (Group B) compared to treated animals (Group A).
- Morphometric analysis showed a significant reduction in lumen area and an increase in medial area in Group A versus Group B.
- The ratio of lumen to medial area was significantly higher in the c-myc antisense oligonucleotide group (2.61+/-0.18) compared to the control group (1.14+/-0.33), P<0.0001.
Conclusions:
- Intraoperative topical application of c-myc antisense oligonucleotides effectively reduces post-operative stenosis.
- This gene silencing strategy demonstrates potential in mitigating vascular remodelling and restenosis.
- Targeting c-myc translation offers a promising therapeutic avenue for improving outcomes after vascular interventions.
