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Persistence of atherosclerotic plaque but reduced aneurysm formation in mice with stromelysin-1 (MMP-3) gene inactivation.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Silence, J. Lupu, Florea Collen, Désiré Lijnen, Henri Roger |
| Copyright Year | 2001 |
| Abstract | To investigate a potential role for stromelysin-1 (MMP-3) in the development and progression of atherosclerotic lesions and aneurysm formation, mice with a deficiency of apolipoprotein E (ApoE(-/-):MMP-3(+/+))) or with a combined deficiency of apoE and MMP-3 (ApoE(-/-):MMP-3(-/-)) were kept on a cholesterol-rich diet for 30 weeks. Atherosclerotic lesions throughout the thoracic aorta were significantly larger in ApoE(-/-):MMP-3(-/-) than in ApoE(-/-):MMP-3(+/+) mice (P<0.05) and contained more fibrillar collagen (P<0.01). Aneurysms in the thoracic and abdominal aortas were less frequent in ApoE(-/-):MMP-3(-/-) than in ApoE(-/-):MMP-3(+/+) mice (8.5+/-1.7% vs 14+/-2.1% of sections, mean+/-SD, P<0.01). Immunocytochemistry revealed enhanced accumulation of macrophages in atherosclerotic lesions of ApoE(-/-):MMP-3(+/+) mice (P<0.01) and expression of urokinase-type plasminogen activator (u-PA) and MMP-3 colocalizing with macrophages. Zymography confirmed the presence of u-PA and MMP-3 activity in extracts of atherosclerotic aortas. These data suggest that plasmin, generated by macrophage-secreted u-PA, activates pro-MMP-3 produced by accumulated macrophages. MMP-3 activity may then contribute to a reduction of plaque size, possibly by degradation of matrix components, and promote aneurysm formation by degradation of the elastica lamina. |
| Starting Page | 602 |
| Ending Page | 602 |
| Page Count | 1 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://atvb.ahajournals.org/content/atvbaha/21/9/1440.full.pdf?download=true |
| PubMed reference number | 11557669v1 |
| Volume Number | 21 |
| Issue Number | 9 |
| Journal | Arteriosclerosis, thrombosis, and vascular biology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Abdominal aorta structure Aneurysm Apolipoprotein E Apolipoproteins Atherosclerosis Cell secretion Chest Cholesterol Collagen Diseases Dental Plaque Immunocytochemistry Large Matrix Metalloproteinase 3 Plasmin Plasminogen Activator Senile Plaques Thoracic aorta Urokinase |
| Content Type | Text |
| Resource Type | Article |
