Normalization of connexin 43 protein levels prevents cellular and functional signs of dystrophic cardiomyopathy in mice.
Neuromuscul Disord
; 28(4): 361-372, 2018 04.
Article
in En
| MEDLINE
| ID: mdl-29477453
ABSTRACT
Duchenne muscular dystrophy (DMD) associated cardiomyopathy remains incurable. Connexin 43 (Cx43) is upregulated and remodeled in the hearts of mdx mice, a mouse model of DMD. Hearts from Wild Type, mdx, and mdxCx43(+/-) mice were studied before (4-6 months) and after (10-15 months) the onset of cardiomyopathy to assess the impact of decreasing Cx43 levels on cardiac pathology in dystrophic mice. Increased connexin 43 protein levels in mdx hearts were not observed in mdxCx43(+/-) hearts. Cx43 remodeling in mdx hearts was attenuated in mdxCx43(+/-) hearts. At time-point 4-6 months, isolated cardiomyocytes from mdx hearts displayed enhanced ethidium bromide uptake, augmented intracellular calcium signals and increased production of reactive oxygen species. These pathological features were improved in mdxCx43(+/-) cardiomyocytes. Isoproterenol-challenged mdxCx43(+/-) mice did not show arrhythmias or acute lethality observed in mdx mice. Likewise, isoproterenol-challenged mdxCx43(+/-) isolated hearts were also protected from arrhythmogenesis. At time-point 10-15 months, mdxCx43(+/-) mice showed decreased cardiac fibrosis and improved ventricular function, relative to mdx mice. These results suggest that normalization of connexin 43 protein levels in mdx mice reduces overall cardiac pathology.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Calcium
/
Connexin 43
/
Muscular Dystrophy, Duchenne
/
Cardiomyopathies
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Neuromuscul Disord
Journal subject:
NEUROLOGIA
Year:
2018
Document type:
Article
Affiliation country:
United States