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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Weiss, Stephen J. Mactaggart, Jason Greiner, Timothy C. Xiong, Wanfen Baxter, B. Timothy Knispel, Rebecca |
| Description | Author Affiliation: Xiong W ( Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, 68198, USA. wxiong@unmc.edu) |
| Abstract | During arterial aneurysm formation, levels of the membrane-anchored matrix metalloproteinase, MT1-MMP, are elevated dramatically. Although MT1-MMP is expressed predominately by infiltrating macrophages, the roles played by the proteinase in abdominal aortic aneurysm (AAA) formation in vivo remain undefined. Using a newly developed chimeric mouse model of AAA, we now demonstrate that macrophage-derived MT1-MMP plays a dominant role in disease progression. In wild-type mice transplanted with MT1-MMP-null marrow, aneurysm formation induced by the application of CaCl2 to the aortic surface was almost completely ablated. Macrophage infiltration into the aortic media was unaffected by MT1-MMP deletion, and AAA formation could be reconstituted when MT1-MMP+/+ macrophages, but not MT1-MMP+/+ lymphocytes, were infused into MT1-MMP-null marrow recipients. In vitro studies using macrophages isolated from either WT/MT1-MMP-/- chimeric mice, MMP-2-null mice, or MMP-9-null mice demonstrate that MT1-MMP alone plays a dominant role in macrophage-mediated elastolysis. These studies demonstrate that destruction of the elastin fiber network during AAA formation is dependent on macrophage-derived MT1-MMP, which unexpectedly serves as a direct-acting regulator of macrophage proteolytic activity. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 3 |
| Volume Number | 284 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2009-01-16 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Aortic Aneurysm, Abdominal Enzymology Elastin Metabolism Macrophages Matrix Metalloproteinase 13 Animals Aorta Pathology Chemically Induced Genetics Calcium Chloride Toxicity Disease Models, Animal Matrix Metalloproteinase 2 Matrix Metalloproteinase 9 Mice Mice, Knockout Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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