Abstract 16216: Thoracic Aortic Aneurysm Development is Attenuated in Mice Deficient in Matrix Type-1 Metalloproteinase
Background: Thoracic aortic aneurysm (TAA) formation in patients is associated with increased protein abundance of the matrix type-1 metalloproteinase (MT1-MMP). Moreover, there is evidence that a temporal increase in MT1-MMP levels occurs in a murine model of TAA, which correlates to progressive aortic dilation. Accordingly, this study tested the hypothesis that targeted deletion of one allele of of MT1-MMP (MT1-MMP+/-) will attenuate TAA formation.
Methods and Results: Baseline (pre-procedural) aortic diameters (computer-assisted digital microscopy) were similar in MT1-MMP+/- mice (787±19 μm; n=33) and littermate wild type mice (817±13 μm; n=24). TAA was induced by application of 0.5 M CaCl2 to the descending thoracic aorta, and mice were randomized to be terminally studied at 2, 4, 8, and 16 weeks following TAA induction (sample sizes at each time point and mouse strain provided in Figure). The change in aortic diameter for each mouse was computed as the percent difference from its own baseline measurement (Figure). Clear aortic dilation was seen in both the wild type and the MT1-MMP+/- mice as early as 2 weeks post TAA induction; however, aortic dilation was attenuated at 4, 8 and 16 weeks post TAA induction in the MT1-MMP+/- group compared to corresponding values in the wild type littermates (Figure ).
Conclusions: These unique results suggest that MT1-MMP plays a causative role in the formation of TAAs in this murine model. Specific therapeutic strategies aimed at MT1-MMP inhibition may reduce or prevent the clinical progression of thoracic aortic aneurysms.
- © 2013 by American Heart Association, Inc.