| First Author | Xiong W | Year | 2009 |
| Journal | J Biol Chem | Volume | 284 |
| Issue | 3 | Pages | 1765-71 |
| PubMed ID | 19010778 | Mgi Jnum | J:145884 |
| Mgi Id | MGI:3836232 | Doi | 10.1074/jbc.M806239200 |
| Citation | Xiong W, et al. (2009) Membrane-type 1 matrix metalloproteinase regulates macrophage-dependent elastolytic activity and aneurysm formation in vivo. J Biol Chem 284(3):1765-71 |
| abstractText | 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. |
