Cardioprotective effects of α‐cardiac actin on oxidative stress in a dilated cardiomyopathy mouse model - Sorbonne Université Access content directly
Journal Articles FASEB Journal Year : 2020

Cardioprotective effects of α‐cardiac actin on oxidative stress in a dilated cardiomyopathy mouse model

Abstract

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 H2O2. 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.
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Dates and versions

hal-02435155 , version 1 (10-01-2020)

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Aude Angelini, Mark‐alexander Gorey, Florent Dumont, Nathalie Mougenot, Maria Chatzifrangkeskou, et al.. Cardioprotective effects of α‐cardiac actin on oxidative stress in a dilated cardiomyopathy mouse model. FASEB Journal, In press, 34 (2), pp.2987-3005. ⟨10.1096/fj.201902389R⟩. ⟨hal-02435155⟩
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