Matrix metalloproteinase-2 production and its binding to the matrix are increased in abdominal aortic aneurysms.
Degradation of the elastic media is a hallmark of abdominal aortic aneurysms (AAAs). We examined the expression of 2 elastolytic matrix metalloproteinases (MMPs), MMP-2 and MMP-9, in AAA aortic tissues compared with those from atherosclerotic occlusive disease (AOD) and nondiseased control tissues....
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
1998
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| _version_ | 1797080822964027392 |
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| author | Davis, V Persidskaia, R Baca-Regen, L Itoh, Y Nagase, H Persidsky, Y Ghorpade, A Baxter, B |
| author_facet | Davis, V Persidskaia, R Baca-Regen, L Itoh, Y Nagase, H Persidsky, Y Ghorpade, A Baxter, B |
| author_sort | Davis, V |
| collection | OXFORD |
| description | Degradation of the elastic media is a hallmark of abdominal aortic aneurysms (AAAs). We examined the expression of 2 elastolytic matrix metalloproteinases (MMPs), MMP-2 and MMP-9, in AAA aortic tissues compared with those from atherosclerotic occlusive disease (AOD) and nondiseased control tissues. Quantitative competitive reverse transcription-polymerase chain reaction and gelatin zymography showed increased MMP-9 mRNA and protein in both AAA and AOD tissues compared with those in control tissue, but there was no significant difference between AAA and AOD. In contrast, MMP-2 mRNA and protein levels were significantly higher in AAA than in AOD or control tissues. Sequential extraction of the MMPs from the aortic tissue with a physiological salt solution, 2% dimethylsulfoxide (DMSO), and 10 mol/L urea showed that large amounts of MMP-2 and MMP-9 were bound to the matrix. The most conspicuous finding was that the levels of MMP-2 were significantly elevated in the DMSO fraction in AAA tissues compared with AOD and control tissues. In addition, a large portion of MMP-2 found in the DMSO and urea fractions was in the active 62-kDa form, indicating that the precursor of MMP-2 in AAA is largely activated locally and binds to the tissue matrix tightly. By immunolocalization, MMP-9 was found to be primarily produced by macrophages and MMP-2 by mesenchymal cells. The production of MMP-2 was prominent when mesenchymal cells were surrounded by inflammatory cells, suggesting paracrine modulation of MMP-2 expression in AAAs. These observations emphasize that MMP-2 participates in the progression of AAAs by degrading aortic tissue matrix components. |
| first_indexed | 2024-03-07T01:05:43Z |
| format | Journal article |
| id | oxford-uuid:8b433cc9-f3a2-4164-af5d-5cc961ddc223 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:05:43Z |
| publishDate | 1998 |
| record_format | dspace |
| spelling | oxford-uuid:8b433cc9-f3a2-4164-af5d-5cc961ddc2232022-03-26T22:37:01ZMatrix metalloproteinase-2 production and its binding to the matrix are increased in abdominal aortic aneurysms.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8b433cc9-f3a2-4164-af5d-5cc961ddc223EnglishSymplectic Elements at Oxford1998Davis, VPersidskaia, RBaca-Regen, LItoh, YNagase, HPersidsky, YGhorpade, ABaxter, BDegradation of the elastic media is a hallmark of abdominal aortic aneurysms (AAAs). We examined the expression of 2 elastolytic matrix metalloproteinases (MMPs), MMP-2 and MMP-9, in AAA aortic tissues compared with those from atherosclerotic occlusive disease (AOD) and nondiseased control tissues. Quantitative competitive reverse transcription-polymerase chain reaction and gelatin zymography showed increased MMP-9 mRNA and protein in both AAA and AOD tissues compared with those in control tissue, but there was no significant difference between AAA and AOD. In contrast, MMP-2 mRNA and protein levels were significantly higher in AAA than in AOD or control tissues. Sequential extraction of the MMPs from the aortic tissue with a physiological salt solution, 2% dimethylsulfoxide (DMSO), and 10 mol/L urea showed that large amounts of MMP-2 and MMP-9 were bound to the matrix. The most conspicuous finding was that the levels of MMP-2 were significantly elevated in the DMSO fraction in AAA tissues compared with AOD and control tissues. In addition, a large portion of MMP-2 found in the DMSO and urea fractions was in the active 62-kDa form, indicating that the precursor of MMP-2 in AAA is largely activated locally and binds to the tissue matrix tightly. By immunolocalization, MMP-9 was found to be primarily produced by macrophages and MMP-2 by mesenchymal cells. The production of MMP-2 was prominent when mesenchymal cells were surrounded by inflammatory cells, suggesting paracrine modulation of MMP-2 expression in AAAs. These observations emphasize that MMP-2 participates in the progression of AAAs by degrading aortic tissue matrix components. |
| spellingShingle | Davis, V Persidskaia, R Baca-Regen, L Itoh, Y Nagase, H Persidsky, Y Ghorpade, A Baxter, B Matrix metalloproteinase-2 production and its binding to the matrix are increased in abdominal aortic aneurysms. |
| title | Matrix metalloproteinase-2 production and its binding to the matrix are increased in abdominal aortic aneurysms. |
| title_full | Matrix metalloproteinase-2 production and its binding to the matrix are increased in abdominal aortic aneurysms. |
| title_fullStr | Matrix metalloproteinase-2 production and its binding to the matrix are increased in abdominal aortic aneurysms. |
| title_full_unstemmed | Matrix metalloproteinase-2 production and its binding to the matrix are increased in abdominal aortic aneurysms. |
| title_short | Matrix metalloproteinase-2 production and its binding to the matrix are increased in abdominal aortic aneurysms. |
| title_sort | matrix metalloproteinase 2 production and its binding to the matrix are increased in abdominal aortic aneurysms |
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