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Cardioprotective effects of α‐cardiac actin on oxidative stress in a dilated cardiomyopathy mouse model
Author(s) -
Angelini Aude,
Gorey MarkAlexander,
Dumont Florent,
Mougenot Nathalie,
Chatzifrangkeskou Maria,
Muchir Antoine,
Li Zhenlin,
Mericskay Mathias,
Decaux JeanFrancois
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201902389r
Subject(s) - oxidative stress , dilated cardiomyopathy , actin , medicine , actin cytoskeleton , nox4 , microbiology and biotechnology , cardiomyopathy , heart failure , biology , cytoskeleton , nadph oxidase , biochemistry , cell
The expression of α‐cardiac actin, a major constituent of the cytoskeleton of cardiomyocytes, is dramatically decreased in a mouse model of dilated cardiomyopathy triggered by inducible cardiac‐specific serum response factor ( Srf ) gene disruption that could mimic some forms of human dilated cardiomyopathy. To investigate the consequences of the maintenance of α‐cardiac actin expression in this model, we developed a new transgenic mouse based on Cre/LoxP strategy, allowing together the induction of SRF loss and a compensatory expression of α‐cardiac actin. Here, we report that maintenance of α‐cardiac actin within cardiomyocytes temporally preserved cytoarchitecture from adverse cardiac remodeling through a positive impact on both structural and transcriptional levels. These protective effects were accompanied in vivo by the decrease of ROS generation and protein carbonylation and the downregulation of NADPH oxidases NOX2 and NOX4. We also show that ectopic expression of α‐cardiac actin protects HEK293 cells against oxidative stress induced by H 2 O 2 . Oxidative stress plays an important role in the development of cardiac remodeling and contributes also to the pathogenesis of heart failure. Taken together, these findings indicate that α‐cardiac actin could be involved in the regulation of oxidative stress that is a leading cause of adverse remodeling during dilated cardiomyopathy development.