Matrix Metalloproteinase-2 Production and Its Binding to the Matrix Are Increased in Abdominal Aortic Aneurysms
| Autor: | Anuja Ghorpade, B T Baxter, Raisa N. Persidskaia, Yoshifumi Itoh, Lisa Baca-Regen, Valerie A. Davis, Hideaki Nagase, Yuri Persidsky |
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| Rok vydání: | 1998 |
| Předmět: |
Pathology
medicine.medical_specialty Gelatin Zymography Gelatinase A Matrix metalloproteinase Matrix (biology) Biology Polymerase Chain Reaction Pathogenesis Paracrine signalling medicine Humans Aorta Abdominal Collagenases RNA Messenger Aged Mesenchymal stem cell Metalloendopeptidases Middle Aged Molecular biology Matrix Metalloproteinase 9 Gelatinases cardiovascular system Matrix Metalloproteinase 2 Immunohistochemistry Cardiology and Cardiovascular Medicine Aortic Aneurysm Abdominal |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 18:1625-1633 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/01.atv.18.10.1625 |
| Popis: | Abstract —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. |
| Databáze: | OpenAIRE |
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