Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Ikonomidis, J.S. et al.

Ikonomidis, Barbour, Amani, Stroud, Herron, McClister, Camens, Lindsey, Mukherjee, Spinale,

Effects of deletion of the matrix metalloproteinase 9 gene on development of murine thoracic aortic aneurysms.

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.[1]

References

Effects of deletion of the matrix metalloproteinase 9 gene on development of murine thoracic aortic aneurysms. Ikonomidis, J.S., Barbour, J.R., Amani, Z., Stroud, R.E., Herron, A.R., McClister, D.M., Camens, S.E., Lindsey, M.L., Mukherjee, R., Spinale, F.G. Circulation (2005) [Pubmed]

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