Journal Article

ATF6beta is not essential for the development of physiological cardiac hypertrophy

Correll, Robert N, Cohen, Caroline T, Schweitzer, Saige, Shokri, Mohammad-Reza, Johnson, Anna Grace, Davis, Emery, Bui, Chuong, Rowland, Mary B, Moore, Patrick E, York, Thomas, Sin, Jon

2025

Overview

Physiological cardiac hypertrophy is a compensatory remodeling of the heart in response to stimuli such as exercise training or pregnancy that is reversible and well-tolerated. We previously described how the activating transcription factor 6 (ATF6) proteins, ATF6[alpha] and ATF6[beta], were required for pathological hypertrophy in response to hemodynamic stress. Here, we examine the functional roles of both ATF6 proteins in the context of exercise-induced physiological hypertrophy. After 20 days of swim training, we found differential roles: whole body gene-deleted mice lacking ATF6[alpha] had an attenuated hypertrophic response compared to wild-type mice but those lacking ATF6[beta] did not. Additionally, mice lacking ATF6[alpha] displayed ventricular dilation and reduced fractional shortening after swimming. While we observed no differences in the expression of downstream UPR signaling between the exercise groups, mice lacking ATF6[alpha] showed enhanced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). Thus, in response to swim training, loss of ATF6[beta] did not hinder the development of physiological hypertrophy, but loss of ATF6[alpha] resulted in significantly reduced cardiac fractional shortening.

• Publisher: Public Library of Science
• Subject: Analysis / Calcineurin / Care and treatment / Comparative analysis / Diagnosis / Dosage and administration / Genes / Genetic aspects / Heart / Heart cells / Heart enlargement / Methods / Mice / Patient monitoring / Pregnancy / Proteins