The expression and localization of membrane type-1 matrix metalloproteinase in human abdominal aortic aneurysms.
BACKGROUND AND OBJECTIVE: Matrix metalloproteinase-2 (MMP-2) degrades both fibrillar collagens and elastin. MMP-2 is secreted as a latent 72-kd proenzyme that must be proteolytically processed to the 62-kd active form. In our laboratory we demonstrated a significant increase of active, matrix-bound...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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2001
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| _version_ | 1797090377087320064 |
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| author | Nollendorfs, A Greiner, T Nagase, H Baxter, B |
| author_facet | Nollendorfs, A Greiner, T Nagase, H Baxter, B |
| author_sort | Nollendorfs, A |
| collection | OXFORD |
| description | BACKGROUND AND OBJECTIVE: Matrix metalloproteinase-2 (MMP-2) degrades both fibrillar collagens and elastin. MMP-2 is secreted as a latent 72-kd proenzyme that must be proteolytically processed to the 62-kd active form. In our laboratory we demonstrated a significant increase of active, matrix-bound MMP-2 in abdominal aortic aneurysmal (AAA) tissue compared with nonaneurysmal aorta with arteriosclerotic occlusive disease and normal aortic tissue. This increase in active MMP-2 is considered to be important in aneurysm pathogenesis, but the mechanism of its activation in aortic tissue is unknown. Membrane type-1 MMP (MT-1 MMP) is known to be an activator of MMP-2. The purpose of this study was to determine MT-1 MMP expression and its involvement in pro-MMP-2 activation in human aneurysmal tissue. METHODS: Infrarenal aortic tissue was obtained during the surgical repair of AAAs or the bypass of aortoiliac occlusive disease, or from nondiseased aorta, and the expression of MT-1 MMP messenger RNA was determined with Northern blot analysis. MT-1 MMP protein was determined with immunoblot and immunohistochemistry. The ability of aortic tissue to activate pro-MMP-2 was analyzed by incubating aortic tissue with exogenous radiolabeled pro-MMP-2. RESULTS: MT-1 MMP messenger RNA and protein are increased in AAA (P <.05) compared with arteriosclerotic occlusive disease and normal aortic tissue. Immunohistochemical analysis localized MT-1 MMP to aortic smooth muscle cells and macrophages in aneurysmal tissue. AAA tissue demonstrated a greater capacity to activate exogenous pro-MMP-2 compared with atherosclerotic and normal aortic tissue (P <.05). CONCLUSION: These studies demonstrate that MT-1 MMP is increased in AAA tissue and suggest that it may be important in AAA pathogenesis through its ability to activate pro-MMP-2 |
| first_indexed | 2024-03-07T03:17:42Z |
| format | Journal article |
| id | oxford-uuid:b65b7b2f-7c45-47da-b819-62b7754976d9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:17:42Z |
| publishDate | 2001 |
| record_format | dspace |
| spelling | oxford-uuid:b65b7b2f-7c45-47da-b819-62b7754976d92022-03-27T04:40:24ZThe expression and localization of membrane type-1 matrix metalloproteinase in human abdominal aortic aneurysms.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b65b7b2f-7c45-47da-b819-62b7754976d9EnglishSymplectic Elements at Oxford2001Nollendorfs, AGreiner, TNagase, HBaxter, B BACKGROUND AND OBJECTIVE: Matrix metalloproteinase-2 (MMP-2) degrades both fibrillar collagens and elastin. MMP-2 is secreted as a latent 72-kd proenzyme that must be proteolytically processed to the 62-kd active form. In our laboratory we demonstrated a significant increase of active, matrix-bound MMP-2 in abdominal aortic aneurysmal (AAA) tissue compared with nonaneurysmal aorta with arteriosclerotic occlusive disease and normal aortic tissue. This increase in active MMP-2 is considered to be important in aneurysm pathogenesis, but the mechanism of its activation in aortic tissue is unknown. Membrane type-1 MMP (MT-1 MMP) is known to be an activator of MMP-2. The purpose of this study was to determine MT-1 MMP expression and its involvement in pro-MMP-2 activation in human aneurysmal tissue. METHODS: Infrarenal aortic tissue was obtained during the surgical repair of AAAs or the bypass of aortoiliac occlusive disease, or from nondiseased aorta, and the expression of MT-1 MMP messenger RNA was determined with Northern blot analysis. MT-1 MMP protein was determined with immunoblot and immunohistochemistry. The ability of aortic tissue to activate pro-MMP-2 was analyzed by incubating aortic tissue with exogenous radiolabeled pro-MMP-2. RESULTS: MT-1 MMP messenger RNA and protein are increased in AAA (P <.05) compared with arteriosclerotic occlusive disease and normal aortic tissue. Immunohistochemical analysis localized MT-1 MMP to aortic smooth muscle cells and macrophages in aneurysmal tissue. AAA tissue demonstrated a greater capacity to activate exogenous pro-MMP-2 compared with atherosclerotic and normal aortic tissue (P <.05). CONCLUSION: These studies demonstrate that MT-1 MMP is increased in AAA tissue and suggest that it may be important in AAA pathogenesis through its ability to activate pro-MMP-2 |
| spellingShingle | Nollendorfs, A Greiner, T Nagase, H Baxter, B The expression and localization of membrane type-1 matrix metalloproteinase in human abdominal aortic aneurysms. |
| title | The expression and localization of membrane type-1 matrix metalloproteinase in human abdominal aortic aneurysms. |
| title_full | The expression and localization of membrane type-1 matrix metalloproteinase in human abdominal aortic aneurysms. |
| title_fullStr | The expression and localization of membrane type-1 matrix metalloproteinase in human abdominal aortic aneurysms. |
| title_full_unstemmed | The expression and localization of membrane type-1 matrix metalloproteinase in human abdominal aortic aneurysms. |
| title_short | The expression and localization of membrane type-1 matrix metalloproteinase in human abdominal aortic aneurysms. |
| title_sort | expression and localization of membrane type 1 matrix metalloproteinase in human abdominal aortic aneurysms |
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