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Chronic vasodilation induces matrix metalloproteinase 9 (MMP-9) expression during microvascular remodeling in rat
1Department of Biomedical Engineering, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Objective:
The process of microvessel growth and remodeling depends on the presence of matrix metalloproteinases (MMPs) in a specific spatial pattern of expression. This study characterizes the spatial distribution of metalloproteinase-9 (MMP-9) expression during microvascular remodeling in the rat spinotrapezius muscle.
Methods:
Female Sprague-Dawley rats (4 weeks old) were administered the alpha1-adrenergic blocker prazosin for 7 days to induce chronic vasodilation and associated increases in capillary and arteriolar density. MMP-9 expression was analyzed by Western blotting analysis of microdissected regions of muscle and immunolabeling of muscle sections.
Results:
Capillary density expressed as both capillary-to-fiber ratio (C/F) and capillaries per mm2 increased significantly (p < 0.01) due to prazosin administration. Western blotting on microdissected regions of spinotrapezius muscle showed that there was an increase in MMP-9 expression in prazosin-treated animals. Additionally, the Western blots showed a presence of the activated form of MMP-9 in regions of spinotrapezius muscle containing vessels on the order of capillaries and small arterioles. Immunohistochemistry demonstrated that MMP-9 significantly increased in the muscles of treated animals in areas within the vessel walls of microvessels greater than 20 microm in diameter. However, interstitial MMP-9 expression did not significantly increase with prazosin administration.
Conclusions:
These results demonstrate that the expression of MMP-9 increases during in vivo microvascular remodeling in adult skeletal muscle. The MMP-9 expression is limited to larger (>20-microm diameter) microvessels, suggesting a role for MMP-9 in the remodeling of such vessels during prazosin-induced vasodilation and the subsequent capillary proliferation.
Insights
Matrix metalloproteinase-9 (MMP-9) expression increases in adult skeletal muscle microvascular remodeling. This study found MMP-9 localized to larger microvessels during prazosin-induced vasodilation and capillary growth.
Area of Science:
- Physiology
- Molecular Biology
- Skeletal Muscle Research
Background:
- Microvessel growth and remodeling are crucial for skeletal muscle function.
- Matrix metalloproteinases (MMPs), particularly MMP-9, play a role in extracellular matrix dynamics during vascular changes.
Purpose of the Study:
- To characterize the spatial distribution of metalloproteinase-9 (MMP-9) expression during microvascular remodeling in rat spinotrapezius muscle.
- To investigate the role of MMP-9 in response to induced vasodilation and increased vascular density.
Main Methods:
- Administration of prazosin to female Sprague-Dawley rats to induce chronic vasodilation and increase capillary density.
- Analysis of MMP-9 expression using Western blotting on microdissected muscle regions and immunohistochemistry on muscle sections.
Main Results:
- Prazosin administration significantly increased capillary density (capillary-to-fiber ratio and capillaries/mm2).
- Western blotting revealed increased MMP-9 expression in prazosin-treated rats, with the activated form present in regions with capillaries and small arterioles.
- Immunohistochemistry showed increased MMP-9 within the vessel walls of microvessels >20 microm in diameter, but not in the interstitium.
Conclusions:
- MMP-9 expression is upregulated during in vivo microvascular remodeling in adult skeletal muscle.
- MMP-9 localization to larger microvessels suggests a specific role in the remodeling of these vessels during adaptive responses like vasodilation and capillary proliferation.