Key result
ATF3 deletion in cardiomyocytes reduced heart growth and dampened fibrosis following transverse aortic constriction, whereas ATF3 ablation in myofibroblasts reduced the hypertrophic gene program.
Why the study?
While transgenic mice with cardiomyocyte ATF3 expression show adverse cardiac remodeling, whole body knockout yielded non-conclusive results, leaving unclear whether cell type-specific ATF3 ablation produces diverse cardiac phenotypes.
Does ablation of ATF3 in cardiomyocytes or myofibroblasts alter the cardiac hypertrophic and fibrotic response to transverse aortic constriction in mice?
Population
Mice with cardiomyocyte- or myofibroblast-specific ATF3 ablation challenged with transverse aortic constriction
Comparison
ATF3 ablation in cardiomyocytes vs myofibroblasts after transverse aortic constriction
Design
Animal experimental study
Follow-up
Eight weeks
Authors
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ATF3 cell-specific targeting merits exploration in pressure-overload models; remains hypothesis-generating pending human data.
Does ablation of ATF3 in cardiomyocytes or myofibroblasts alter the cardiac hypertrophic and fibrotic response to transverse aortic constriction in mice?
ATF3 expression in the heart plays a key role in the maladaptive response to pressure overload, with distinct roles in cardiomyocytes (promoting cardiac growth and fibrosis) and myofibroblasts (promoting a hypertrophic gene program).
Abu-Sharki et al. (2020) studied Cardiac remodeling and hypertrophy (pressure overload). ATF3 ablation in cardiomyocytes or myofibroblasts vs. ATF3-flox control mice was evaluated on Ventricle weight to body weight ratio (VW/BW) and hypertrophic/fibrotic gene expression. ATF3 deletion in cardiomyocytes reduced heart growth and dampened fibrosis following transverse aortic constriction, whereas ATF3 ablation in myofibroblasts reduced the hypertrophic gene program.