A Murine Model of Stent Implantation in the Carotid Artery for the Study of Restenosis
May 14th, 2013
A model of stent implantation in mouse carotid artery is described. Compared to other similar methods, this procedure is very rapid, simple and accessible, offering the possibility to study in a convenient way the vascular wall reaction to different drug-eluting stents and the molecular mechanisms of restenosis.
The overall goal of this procedure is to implant a stent into the mouse carotid artery that allows for the study of vessel remodeling or the effects of different drug coatings. First, the stent is prepared for implantation by transferring it into a silicone tube. Next, the common artery is isolated and sutures are put in place to interrupt the blood flow.
The stent is then introduced through a small incision on the external carotid artery. Once in place, the silicone tube and guide wire are removed, leaving the stent in the common carotid artery. Ultimately, samples are stained with gemsa for the analysis of plaque formation.
Existing model for instant restenosis in misa difficult, they require precise surgical skills and common complication and splitting or paralyzes. The risk is complication is minimizing our model by keeping the stent in view throughout the implantation procedure demonstrated. Parts of this procedure will be Dr.Simsek Imas postdoc from our laboratory father.
I will demonstrate the implantation of the stent into the cartridge artery. Begin by using forceps to transfer the stent to a two centimeter silicone tube. Stopping two millimeters short of the front end, the exposed end of the tube should be cut diagonally for easier implantation moisten the stent before implantation to make insertion easier.
Next, confirm the proper depth of anesthesia in an adult male mouse. After applying protective ointment to the eyes, shave the ventral neck area. Next, clean the site with repeated rubbings of Betadine and alcohol working under a stereo microscope.
Use scissors to make a small median incision over the area. Separate through the fat and tissue until the left common carotid artery is isolated. Once visualized, tie a suture around the common artery, approximately one centimeter from the bifurcation.
Tie two sutures around the external carotid artery, leaving the distal knot loose to age in stent implantation. Next, tie a suture around the internal carotid artery. After the sutures are secured, make a small incision in the external artery near the proximal knot.
Using a guide wire, introduce the silicone tube containing the stent. Once in place, remove the silicone tube to allow the stent to expand. Next, tighten the distal knot on the external carotid artery and remove the sutures on the internal and common carotid artery to restore blood flow.
Close the incision with suture clips and place the animal under a warming lamp. Until fully recovered. Word plaque formation is examined at different time points after stent implantation.
First after euthanasia and trans cardial perfusion, isolate the left carotid artery and remove the portion containing the stent. Place the sample into 4%PFA solution. At least 16 hours later, embed the sample in plastic as shown here.
After cutting 50 micrometer thick sections with a diamond band saw performed gem sustaining to evaluate plaque formation. Microcomputer tomography imaging performed one week after stent implantation showed that the stent was not dislocated by blood flow. No vessel or endothelial damage was found in untented areas of the vessel, as shown by Odin blue and endothelial specific CD 31 staining histological staining is used to study the extent of plaque formation.
Here the stent is visible as the black stained fibrin inside the neointima. In some cases, a complete occlusion of the vessel is observed. The reendothelialization of the stent struts is shown on the left by the double arrow, while the incomplete luminal reendothelialization is shown on the right by a single arrow.
While attempting this procedure, it is important to remember that the operating area should be constantly watered to prevent drying and to make manipulating the stent easier.
Overview
This article describes a model for stent implantation in the mouse carotid artery, which is rapid and accessible for studying vascular wall reactions to drug-eluting stents and restenosis mechanisms.
Key Study Components
Area of Science
- Neuroscience
- Vascular Biology
- Cardiovascular Research
Background
- Stent implantation models are crucial for studying vascular responses.
- Existing models often require advanced surgical skills and have high complication rates.
- This model aims to minimize complications while allowing for effective study.
- The procedure is demonstrated by Dr. Simsek Imas from the laboratory.
Purpose of Study
- To develop a simple and rapid stent implantation technique in mice.
- To investigate the effects of different drug coatings on vessel remodeling.
- To analyze plaque formation and restenosis mechanisms post-implantation.
Methods Used
- Preparation of the stent using a silicone tube for implantation.
- Isolation of the common carotid artery and suturing to control blood flow.
- Insertion of the stent through a small incision in the external carotid artery.
- Histological analysis of plaque formation using Giemsa staining.
Main Results
- Micro-computed tomography confirmed stent stability post-implantation.
- No significant vessel or endothelial damage was observed.
- Histological staining revealed the extent of plaque formation.
- Reendothelialization of stent struts was documented.
Conclusions
- The described model is effective for studying stent implantation and restenosis.
- It minimizes complications associated with traditional methods.
- This approach can facilitate further research into vascular responses and treatments.
Frequently Asked Questions
Executive Industry Relevance
This murine carotid stent implantation model provides a rapid, accessible system for studying vascular responses to drug-eluting stents and restenosis mechanisms. It enables preclinical evaluation of stent coatings and vascular remodeling processes with reduced surgical complexity and complication rates. The model supports target validation and mechanistic de-risking in cardiovascular drug development pipelines.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Scientific Value: Enables interrogation of therapeutic hypotheses related to vascular injury and repair pathways.
- Scientific Value: Supports functional validation of molecular targets involved in restenosis and neointimal formation.
- Operational Value: Offers a reproducible murine model with minimized complications for consistent target engagement studies.
Screening & Assay Development
- Scientific Value: Provides a standardized platform for evaluating drug-coated stents and their impact on plaque formation.
- Operational Value: Facilitates assay standardization through Giemsa staining and histological quantification of neointimal hyperplasia.
- Operational Value: Enables scalable screening of stent designs and coating formulations using micro-CT and immunohistochemical readouts.
Translational & Preclinical Research
- Scientific Value: Models human carotid artery stenting pathophysiology for translational biomarker discovery.
- Scientific Value: Supports preclinical assessment of drug-eluting stent efficacy and safety profiles.
- Operational Value: Promotes continuity from discovery to preclinical validation through standardized vessel preparation and analysis workflows.
Pipeline & Workflow Integration
The model integrates into the cardiovascular discovery continuum from target validation through lead identification to preclinical efficacy testing, enabling iterative design of stent-based interventions.
- Discovery Biology: Supports pathway clarification of vascular remodeling mechanisms following stent-induced injury.
- Screening: Delivers quantitative outputs via plaque area measurement and reendothelialization scoring for compound comparison.
- Analytics: Generates histological and imaging readouts that enable statistical comparison of stent performance across conditions.
- Translational Research: Aligns with preclinical continuity by modeling human-relevant restenosis processes in a murine system.
- Enterprise Reuse: Establishes a reusable platform for iterative stent design evaluation across multiple therapeutic programs.
Operational & Enterprise Impact
- Scientific Value: Enhances predictive confidence in stent-biological interactions by reducing mechanistic ambiguity in restenosis pathways.
- Operational Value: Improves reproducibility through standardized surgical technique and controlled blood flow interruption.
- Strategic Value: Informs go/no-go decisions by providing early efficacy and safety signals for stent coatings.
- Portfolio Impact: Enables risk-adjusted prioritization of stent development candidates based on restenosis suppression potential.
Implementation Considerations
- Requires expertise in microsurgical techniques and vascular dissection under stereo microscopy.
- Dependent on instrumentation including silicone tubing, guide wires, suture materials, and diamond band saw for sectioning.
- Necessitates histological infrastructure for Giemsa staining, immunohistochemical labeling (e.g., CD31), and microscopy analysis.
- Involves adaptation considerations when translating findings to larger animal models or human-relevant systems.
- Limited by murine scale, which may constrain certain device sizes and imaging resolutions compared to clinical applications.
