| First Author | Ikonomidis JS | Year | 2005 |
| Journal | Circulation | Volume | 112 |
| Issue | 9 Suppl | Pages | I242-8 |
| PubMed ID | 16159824 | Mgi Jnum | J:116808 |
| Mgi Id | MGI:3695063 | Doi | 10.1161/CIRCULATIONAHA.104.526152 |
| Citation | Ikonomidis JS, et al. (2005) Effects of deletion of the matrix metalloproteinase 9 gene on development of murine thoracic aortic aneurysms. Circulation 112(9 Suppl):I242-8 |
| abstractText | BACKGROUND: The matrix metalloproteinases (MMPs) contribute to cardiovascular remodeling, and MMPs, such as the gelatinases (MMP-9 and MMP-2), have been identified in thoracic aortic aneurysmal (TAA) tissue, but a cause-effect relationship has not been clearly established. Accordingly, this study examined TAA progression in mice devoid of the MMP-9 gene. METHODS AND RESULTS: The descending thoracic aortas of wild-type (WT) FVB (n =17) and MMP-9 gene knockout (KO, n =11) mice were exposed to 0.5 mol/L of CaCl2 for 15 minutes with terminal studies performed at 4 weeks. Aortic lumen diameter was measured using video micrometry at baseline and at 4 weeks (TAA) followed by aortic tissue analysis. In WT mice, aortic diameter increased by 138+/-5% at 4 weeks (P<0.05), consistent with TAA formation. In the KO mice, aortic diameter increased from baseline by 120+/-4% (P<0.05) but was attenuated from WT TAA values (P<0.05). Gelatin zymography performed on TAA segments confirmed the absence of MMP-9 in the KO mice but a >8-fold relative increase in the active form of MMP-2 compared with WT (P<0.05). Despite this, MMP-2 activity was relatively increased (P<0.05) and colocalized to smooth muscle cell actin in a differential pattern favoring medial distruction in the WT TAA compared with the KO TAA segments. CONCLUSIONS: These results demonstrate that MMP-9 gene deletion attenuated TAA formation despite an increase in the zymographic levels of MMP-2. These unique findings suggest that an interaction between these 2 MMPs is necessary to facilitate TAA progression. |
