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DMD-Associated Cardiomyopathy: A Novel Mode of Cardiac Remodeling

AJAS · 2018 Biomedical and Health Sciences (inferred)

Jacob Mammen

Overview

Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disease resulting from mutations in the dystrophin gene and it affects 1 in 5,000 males. In 2017, DMD-associated cardiomyopathy is the leading cause of premature deaths. Clinical data suggests DMD patients develop cardiac atrophy. The hypothesis of this study is DMD-associated cardiomyopathy develops secondary to dysregulation of signaling pathways involved in cardiomyocyte proliferation and cardiac atrophy. Methods: To test the study’s hypothesis, mdx mice, a murine model of DMD, were used. Histological, molecular and transcriptome analyses were undertaken to compare mdx to non-transgenic (NTg) or control hearts at various postnatal time points (P1, P4, P7, 2-week, 4-week and 8-week). Results: mdx mice have decreased heart size with diminished heart/body weight ratios, as compared to NTg controls (4.68 ± 0.07 vs. 5.10 ± 0.07, mdx vs. NTg, p<0.005, n=11 at 8 weeks). Immunohistochemical data reveal similar cardiomyocyte cell size (0.078 ± 0.001 vs. 0.078 ± 0.002, NTg vs. mdx, p=NS, n=3), suggesting there are fewer cells in mdx hearts. Transcriptome profiling revealed a significant reduction in proliferative markers with a corresponding increase in atrophy gene expression in mdx hearts. FACS analysis revealed mdx hearts have fewer cells than NTg hearts. Finally, mdx hearts have reduced protein expression of proliferation markers (Ki67 and pH3). Conclusion: Collectively, the study confirmed mdx mice have small, atrophic hearts due to dysregulation of cardiac proliferative and atrophic signaling pathways. This study sets the stage for investigation into novel therapeutic targets for the ame

Competition history

  • AJAS 2018 Category not listed

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Source: AAAS Annual Meeting (Confex) / American Junior Academy of Science

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