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Updated: May 2, 2026
Transverse Aortic Constriction in Mice
Published on: April 21, 2010
ATF6β is not essential for the development of physiological cardiac hypertrophy
Emery Davis1, Mohammad-Reza Shokri1, Mary B Rowland1
1Department of Biological Sciences, University of Alabama, Tuscaloosa, Alabama, United States of America.
Insights
Activating transcription factor 6 alpha (ATF6α) is crucial for physiological cardiac hypertrophy in response to exercise. Loss of ATF6α impairs heart function, while ATF6β is not essential for this adaptive response.
Area of Science:
- Cardiovascular Physiology
- Molecular Biology
- Gene Regulation
Background:
- Physiological cardiac hypertrophy is a beneficial heart adaptation to stimuli like exercise.
- Activating transcription factor 6 (ATF6) proteins, ATF6α and ATF6β, were previously linked to pathological cardiac hypertrophy.
- The roles of ATF6α and ATF6β in physiological hypertrophy remain unclear.
Purpose of the Study:
- To investigate the functional roles of ATF6α and ATF6β in exercise-induced physiological cardiac hypertrophy.
- To determine if ATF6 proteins are necessary for adaptive cardiac remodeling in response to swim training.
Main Methods:
- Utilized whole-body gene-deleted mice lacking ATF6α or ATF6β.
- Subjected mice to 20 days of swim training.
- Assessed cardiac hypertrophy, ventricular dimensions, fractional shortening, and ERK1/2 phosphorylation.
Main Results:
- Mice lacking ATF6α exhibited an attenuated hypertrophic response and reduced fractional shortening after swim training.
- Loss of ATF6β did not significantly affect the hypertrophic response to swim training.
- Mice lacking ATF6α showed enhanced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation.
Conclusions:
- ATF6α plays a critical role in mediating physiological cardiac hypertrophy and maintaining cardiac function during exercise.
- ATF6β is not essential for exercise-induced physiological cardiac hypertrophy.
- Differential roles of ATF6α and ATF6β in cardiac adaptation to stress warrant further investigation.
Abstract:
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, ATF6α and ATF6β, 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 ATF6α had an attenuated hypertrophic response compared to wild-type mice but those lacking ATF6β did not. Additionally, mice lacking ATF6α 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 ATF6α showed enhanced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). Thus, in response to swim training, loss of ATF6β did not hinder the development of physiological hypertrophy, but loss of ATF6α resulted in significantly reduced cardiac fractional shortening.
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