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Updated: Nov 21, 2025
A Murine Model of Stent Implantation in the Carotid Artery for the Study of Restenosis
Published on: May 14, 2013
Distribution and Dynamic Changes in Matrix Metalloproteinase (MMP)-2, MMP-9, and Collagen in an In Stent Restenosis
Jing Shen1, Jian-Bo Song2, Jun Fan3
1Department of Intervention, Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China; Department of Intervention, Shanxi Provincial People's Hospital, Taiyuan, Shanxi, China.
Objective:
The aim of this study was to observe the spatial distribution and dynamic changes of matrix metalloproteinase (MMP)-2, MMP-9, and collagen in in stent restenosis (ISR) and to explore their influence on ISR.
Methods:
Sixty Z type stents were implanted into the common iliac arteries of minipigs, which were divided into 10 groups (six in each group) according to euthanasia time (6 hours, and 1, 3, 7, 14, 28, 56, 84, 168, and 336 days). After the samples were harvested, haematoxylin and eosin staining, immunohistochemical staining, Western blotting, and Picrosirius red staining were performed for all groups.
Results:
ISR occurred in all six minipigs in the 56 day group (percentage diameter stenosis range 71.6%-79.2%, mean ± standard deviation 75.6% ± 2.5%). The percentage diameter stenosis decreased to 38.3% ± 2.7% at 336 days (p < .001). Immunohistochemical staining showed that MMP-2 and MMP-9 were strongly stained near the internal elastic lamina or in the damaged parts of the intima, around the struts and neointimal lumen surface in the ISR process. The expression of MMP-2 and MMP-9 at 56 days was significantly lower compared with their peaks (seven days and one day [p < .001; p = .002], respectively). At 56 days, the collagen content reached its maximum (mean integrated optical density range 0.73-0.92, mean ± standard deviation 0.82 ± 0.09). From the 14 day group to the 336 day group, mature collagen in neointima was correlated negatively with MMP-2 (γ(36) = -0.816; p < .001) and MMP-9 expression (γ(36) = -0.853; p < .001). During the neointimal regression period, new collagen in neointima was positively correlated with MMP-2 (γ(24) = 0.683; p < .001) and MMP-9 (γ(24) = 0.873; p < .001).
Conclusion:
This study has demonstrated the spatial distribution of and dynamic changes in MMP-2, MMP-9, and collagen in ISR by simulating the process of neointima from generation to regression after stent implantation. When ISR occurred, MMP-2 and MMP-9 expression decreased and collagen content reached its maximum, which might contribute to ISR.
Insights
In in stent restenosis (ISR), matrix metalloproteinase (MMP)-2 and MMP-9 expression decreases as collagen content peaks, potentially contributing to the condition. This study tracked these changes over time in a minipig model.
Area of Science:
- Cardiovascular Research
- Biomedical Engineering
- Pathology
Background:
- In stent restenosis (ISR) is a significant complication following angioplasty.
- Understanding the molecular mechanisms, particularly the roles of matrix metalloproteinases (MMPs) and collagen, is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the spatial distribution and dynamic changes of MMP-2, MMP-9, and collagen during ISR.
- To explore the influence of these factors on the development and regression of ISR.
Main Methods:
- Implantation of Z type stents into minipig common iliac arteries.
- Harvesting of samples at various time points (6 hours to 336 days).
- Analysis using hematoxylin and eosin staining, immunohistochemistry, Western blotting, and Picrosirius red staining.
Main Results:
- ISR peaked around 56 days, with subsequent regression observed by 336 days.
- MMP-2 and MMP-9 expression peaked early and decreased as collagen content maximized during ISR.
- Collagen content showed a negative correlation with MMP-2 and MMP-9 during the mature neointima phase and a positive correlation during neointimal regression.
Conclusions:
- The study elucidates the dynamic interplay between MMPs and collagen in ISR.
- Decreased MMP expression and increased collagen content coincide with ISR development, suggesting their contribution to the condition.
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