Nf-Îºb Inhibition Rescues Cardiac Function By Remodeling Calcium Genes In A Duchenne Muscular Dystrophy Model
Duchenne muscular dystrophy (DMD) is a neuromuscular disorder causing progressive muscle degeneration. Although cardiomyopathy is a leading mortality cause in DMD patients, the mechanisms underlying heart failure are not well understood. Previously, we showed that NF-ÎºB exacerbates DMD skeletal muscle pathology by promoting inflammation and impairing new muscle growth. Here, we show that NF-ÎºB is activated in murine dystrophic (mdx) hearts, and that cardiomyocyte ablation of NF-ÎºB rescues cardiac function. This physiological improvement is associated with a signature of upregulated calcium genes, coinciding with global enrichment of permissive H3K27 acetylation chromatin marks and depletion of the transcriptional repressors CCCTC-binding factor, SIN3 transcription regulator family member A, and histone deacetylase 1. In this respect, in DMD hearts, NF-ÎºB acts differently from its established role as a transcriptional activator, instead promoting global changes in the chromatin landscape to regulate calcium genes and cardiac function.
Digital Object Identifier (DOI)
Peterson, Jennifer M.; Wang, David J.; Shettigar, Vikram; Roof, Steve R.; Canan, Benjamin D.; Bakkar, Nadine; Shintaku, Jonathan; Gu, Jin Mo; Little, Sean C.; Ratnam, Nivedita M.; Londhe, Priya; Lu, Leina; Gaw, Christopher E.; Petrosino, Jennifer M.; Liyanarachchi, Sandya; Wang, Huating; Janssen, Paul M.L.; Davis, Jonathan P.; Ziolo, Mark T.; Sharma, Sudarshana M.; and Guttridge, Denis C., "Nf-Îºb Inhibition Rescues Cardiac Function By Remodeling Calcium Genes In A Duchenne Muscular Dystrophy Model" (2018). Translational Neuroscience. 3.