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Updated: Aug 19, 2026
A Rat Carotid Artery Pressure-Controlled Segmental Balloon Injury with Periadventitial Therapeutic Application
Published on: July 9, 2020
Cytomegalovirus aggravates intimal hyperplasia in rats by stimulating smooth muscle cell proliferation
Geoffrey Kloppenburg1, Rick de Graaf, Selma Herngreen
1Department of Medical Microbiology and Maastricht Infection Centre, University Hospital Maastricht, P. Debyelaan 25, P.O. Box 5800, 6202 AZ Maastricht, the Netherlands.
Abstract:
Epidemiological and animal studies suggest a role for cytomegalovirus (CMV) in restenosis. Previously, we demonstrated that proliferating smooth muscle cells (SMCs) in the injured arterial wall are particularly susceptible to CMV-induced effects. Therefore, we hypothesised that, depending on the time point of infection after vascular injury, CMV infection may affect cell proliferation either in the media or in the neointima, thereby aggravating the process of restenosis. In the present study, we focused on the individual layers of the arterial wall by evaluating, besides the neointima-to-media ratio, the medial and neointimal area and cellularity in the rat femoral artery. Vascular injury was photochemically induced in rat femoral arteries. Immediately or 14 days thereafter, rats were infected with rat CMV (RCMV) or mock infected. The presence of RCMV in the vascular wall was determined at 3, 5, 14 and 35 days after infection by quantitative real-time PCR. When rats were infected immediately after injury, a significant increase was seen only in the medial but not in the neointimal cross-sectional area. On the other hand, when rats were infected 14 days after the initial injury, a significant increase was only seen in the neointimal area, thereby confirming our hypothesis that RCMV infection primary affects proliferating SMCs. As the mean number of SMCs per microm2 in both cell layers was unchanged despite an increase in cross-sectional area, this implies that RCMV stimulated SMC proliferation. Furthermore, these vascular effects were observed without the virus being abundantly present in the vascular wall, suggesting that inflammatory and immune-mediated responses to RCMV infection are more important in aggravating the response to vascular injury than the virus itself.
Insights
Cytomegalovirus (CMV) infection timing impacts arterial smooth muscle cell proliferation after injury. Early CMV infection affects the media, while later infection impacts the neointima, potentially worsening restenosis.
Area of Science:
- Vascular biology
- Virology
- Immunology
Background:
- Cytomegalovirus (CMV) is implicated in restenosis.
- Proliferating smooth muscle cells (SMCs) in injured arteries are susceptible to CMV.
- CMV infection timing may influence restenosis development.
Purpose of the Study:
- To investigate the effect of rat cytomegalovirus (RCMV) infection timing on arterial wall layers after vascular injury.
- To determine if RCMV influences medial or neointimal smooth muscle cell proliferation and area.
- To understand the role of viral presence versus immune response in RCMV-aggravated vascular injury.
Main Methods:
- Photochemical induction of vascular injury in rat femoral arteries.
- Rats were infected with RCMV or mock infected immediately or 14 days post-injury.
- Quantitative real-time PCR assessed RCMV presence; medial and neointimal areas and cellularity were measured.
Main Results:
- RCMV infection immediately post-injury increased medial area but not neointimal area.
- RCMV infection 14 days post-injury increased neointimal area but not medial area.
- Increased vascular area occurred without changes in cell density, indicating stimulated SMC proliferation; effects were seen with low viral load.
Conclusions:
- RCMV infection timing dictates its impact on specific arterial wall layers.
- RCMV stimulates SMC proliferation in a time-dependent manner, affecting either the media or neointima.
- Immune-mediated responses, rather than high viral load, likely drive RCMV's role in exacerbating vascular injury response.
