Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6041281 | Neuromuscular Disorders | 2012 | 9 Pages |
Abstract
Cardiomyopathy is a significant component in Duchenne muscular dystrophy. Although mdx mice are deficient in dystrophin, they only develop mild indicators of cardiomyopathy before 1Â year-of-age, making therapeutic investigations using this model lengthy. In contrast, mdx mice also lacking utrophin (utrnâ/â;mdx) show severely reduced cardiac contractile function and histological indicators of cardiomyopathy by 8-10Â weeks-of-age. Here we demonstrate that utrnâ/â;mdx mice show a similar pattern of cardiac damage to that in dystrophic patients. Matrix metalloproteinases required for ventricular remodeling during the evolution of heart failure are upregulated in utrnâ/â;mdx mice concurrent with the onset of cardiac pathology by 10Â weeks-of-age. Matrix metalloproteinase activity is further dysregulated due to reduced levels of endogenous tissue inhibitors and co-localizes with fibroblasts and collagen I-containing scars. utrnâ/â;mdx mice are therefore a very useful model for investigating potential cardiac therapies.
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Authors
Dawn A. DelfÃn, Kara E. Zang, Kevin E. Schill, Nikita T. Patel, Paul M.L. Janssen, Subha V. Raman, Jill A. Rafael-Fortney,