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Increased matrix metalloproteinase 2 expression in vascular smooth muscle cells cultured from abdominal aortic
M Crowther1, S Goodall, J L Jones
1Department of Surgery and the Department of Pathology, University of Leicester, Leicester, United Kingdom.
Objectives:
Recent evidence has implicated matrix metalloproteinase 2 (MMP-2) in the pathogenesis of aneurysms. The aim of this study was to examine MMP-2 production and expression by aortic smooth muscle cells (SMCs) and dermal fibroblasts derived from patients with abdominal aortic aneurysms (AAAs).
Methods:
Aortic SMCs and dermal fibroblasts were cultured from patients with AAAs or from age-matched controls with atherosclerosis. The production of MMP and tissue inhibitor of metalloproteinase into culture media was analyzed with the use of gelatin zymography, Western blotting, and enzyme-linked immunosorbent assay. Gene expression was analyzed with Northern blotting.
Results:
All cells studied constitutively produced MMP-2. Aortic SMCs cultured from aneurysmal tissue expressed MMP-2 protein and messenger RNA at a significantly higher level than SMCs from controls (P =.008). Dermal fibroblasts from patients with AAAs expressed MMP-2 at a similar level to controls. In both cell types, tissue inhibitor of metalloproteinase 2 and membrane type 1-MMP were expressed at similar levels.
Conclusions:
These data suggested that the regulation of MMP-2 gene expression was altered in the aortic SMCs of patients with aneurysms, but this finding was not repeated in other mesenchymal tissue.
Insights
Matrix metalloproteinase 2 (MMP-2) gene expression is altered in aortic smooth muscle cells (SMCs) from abdominal aortic aneurysm (AAA) patients. This heightened MMP-2 production in aortic SMCs may contribute to AAA pathogenesis.
Area of Science:
- Vascular Biology
- Biochemistry
- Genetics
Background:
- Matrix metalloproteinase 2 (MMP-2) is implicated in aneurysm pathogenesis.
- Abdominal aortic aneurysms (AAAs) involve complex molecular changes in aortic tissue.
Purpose of the Study:
- To investigate MMP-2 production and gene expression in aortic smooth muscle cells (SMCs) and dermal fibroblasts from AAA patients.
- To compare these findings with age-matched controls.
Main Methods:
- Cultured aortic SMCs and dermal fibroblasts from AAA patients and controls.
- Analyzed MMP-2 protein and messenger RNA levels using gelatin zymography, Western blotting, ELISA, and Northern blotting.
Main Results:
- All cells constitutively produced MMP-2.
- Aortic SMCs from AAA patients showed significantly higher MMP-2 protein and mRNA expression compared to controls (P =.008).
- Dermal fibroblasts from AAA patients exhibited similar MMP-2 levels to controls.
Conclusions:
- MMP-2 gene expression regulation appears altered specifically in aortic SMCs of AAA patients.
- This altered regulation was not observed in dermal fibroblasts, suggesting tissue-specific changes.