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Updated: Feb 4, 2026

Implantation of a Carotid Cuff for Triggering Shear-stress Induced Atherosclerosis in Mice
Published on: January 13, 2012
Molecular imaging of MMP activity discriminates unstable from stable plaque phenotypes in shear-stress induced murine
Robert Seifert1,2, Michael T Kuhlmann1, Sarah Eligehausen1
1European Institute for Molecular Imaging (EIMI), University of Münster, Münster, Germany.
Purpose:
As atherosclerotic plaque ruptures are the primary cause of ischaemic events, their preventive identification by imaging remains a clinical challenge. Matrix metalloproteinases (MMP) are involved in plaque progression and destabilisation and are therefore promising targets to characterize rupture-prone unstable plaques. This study aims at evaluating MMP imaging to discriminate unstable from stable plaque phenotypes.
Methods:
ApoE deficient mice (ApoE-/-) on a high cholesterol diet underwent implantation of a tapered cuff around the right common carotid artery (CCA) inducing a highly inflamed atherosclerotic plaque upstream (US) and a more stable plaque phenotype downstream (DS) of the cuff. 8 weeks after surgery, the MMP inhibitor-based photoprobe Cy5.5-AF443 was administered i.v. 3h prior to in situ and ex vivo fluorescence reflectance imaging of the CCAs. Thereafter, CCAs were analysed regarding plaque size, presence of macrophages, and MMP-2 and MMP-9 concentrations by immunohistochemistry and ELISA.
Results:
We found a significantly higher uptake of Cy5.5-AF443 in US as compared to DS plaques in situ (1.29 vs. 1.06 plaque-to-background ratio; p<0.001), which was confirmed by ex vivo measurements. Immunohistochemistry revealed a higher presence of macrophages, MMP-2 and MMP-9 in US compared to DS plaques. Accordingly, MMP-2 concentrations were significantly higher in US plaques (47.2±7.6 vs. 29.6±4.6 ng/mg; p<0.05).
Conclusions:
In the ApoE-/- cuff model MMP-2 and MMP-9 activities are significantly higher in upstream low shear stress-induced unstable atherosclerotic plaques as compared to downstream more stable plaque phenotypes. MMP inhibitor-based fluorescence molecular imaging allows visualization of these differences in shear stress-induced atherosclerosis.
Insights
Matrix metalloproteinase (MMP) imaging effectively identified unstable atherosclerotic plaques in mice. This molecular imaging approach visualizes differences in MMP activity, aiding in the characterization of rupture-prone plaques.
Area of Science:
- Cardiovascular Research
- Molecular Imaging
- Biomedical Engineering
Background:
- Atherosclerotic plaque rupture is a major cause of ischemic events.
- Identifying unstable plaques for prevention is a clinical challenge.
- Matrix metalloproteinases (MMPs) are implicated in plaque destabilization.
Purpose of the Study:
- To evaluate MMP imaging for discriminating unstable from stable atherosclerotic plaque phenotypes.
- To assess the utility of MMP inhibitor-based photoprobes in atherosclerosis research.
Main Methods:
- ApoE deficient mice were used with a cuff model to induce unstable (upstream) and stable (downstream) plaques.
- MMP inhibitor-based photoprobe (Cy5.5-AF443) was administered intravenously.
- In situ and ex vivo fluorescence reflectance imaging, immunohistochemistry, and ELISA were performed.
Main Results:
- Significantly higher Cy5.5-AF443 uptake was observed in unstable plaques compared to stable plaques.
- Unstable plaques showed increased presence of macrophages, MMP-2, and MMP-9.
- MMP-2 concentrations were significantly elevated in unstable plaques.
Conclusions:
- MMP-2 and MMP-9 activities are significantly higher in unstable atherosclerotic plaques.
- MMP inhibitor-based fluorescence molecular imaging can visualize differences in shear stress-induced atherosclerosis.
- This imaging modality holds promise for characterizing rupture-prone plaques.
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