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Updated: Jun 26, 2026
In Vitro Assessment of Cardiac Function Using Skinned Cardiomyocytes
Published on: June 22, 2020
Muscle ring finger 1 mediates cardiac atrophy in vivo
Monte S Willis1, Mauricio Rojas, Luge Li
1Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill, North Carolina, USA. monte_willis@med.unc.edu
Insights
Muscle ring finger-1 (MuRF1) is essential for cardiac atrophy. Mice lacking MuRF1 showed resistance to cardiac atrophy after hypertrophy reversal and with dexamethasone, indicating MuRF1
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Physiology
Background:
- Pathological cardiac hypertrophy, a precursor to heart failure, can be reversed, reducing cardiovascular risk.
- Muscle ring finger-1 (MuRF1), a muscle-specific protein, was previously found to inhibit pathological cardiac hypertrophy.
- Increased cardiac MuRF1 expression is observed during therapeutic cardiac atrophy.
Purpose of the Study:
- To investigate the role of MuRF1 in cardiac atrophy.
- To determine if MuRF1 is essential for the regression of cardiac hypertrophy and dexamethasone-induced cardiac atrophy in vivo.
Main Methods:
- Utilized two mouse models of cardiac atrophy: transaortic constriction (TAC) reversal and dexamethasone administration.
- Employed echocardiography, histology, and gene expression analysis to assess cardiac mass, cardiomyocyte size, and hypertrophic gene markers.
- Compared MuRF1 knockout (MuRF1(-/-)) mice with wild-type littermates.
Main Results:
- MuRF1(-/-) mice exhibited significantly reduced atrophy (approx. 70% less decrease in cardiac mass and cardiomyocyte size) compared to wild-type mice after TAC reversal.
- Wild-type mice recovered baseline cardiac dimensions within 4 days of TAC release, while MuRF1(-/-) mice showed delayed atrophy.
- MuRF1(-/-) mice were resistant to dexamethasone-induced cardiac atrophy.
- Transcriptional activation of hypertrophy markers was similarly attenuated in both genotypes post-TAC release.
Conclusions:
- MuRF1 is essential for mediating cardiac atrophy in vivo.
- MuRF1 plays a critical role in the therapeutic regression of cardiac hypertrophy.
- MuRF1 is required for dexamethasone-induced cardiac atrophy.
Abstract:
Pathological cardiac hypertrophy, induced by various etiologies such as high blood pressure and aortic stenosis, develops in response to increased afterload and represents a common intermediary in the development of heart failure. Understandably then, the reversal of pathological cardiac hypertrophy is associated with a significant reduction in cardiovascular event risk and represents an important, yet underdeveloped, target of therapeutic research. Recently, we determined that muscle ring finger-1 (MuRF1), a muscle-specific protein, inhibits the development of experimentally induced pathological; cardiac hypertrophy. We now demonstrate that therapeutic cardiac atrophy induced in patients after left ventricular assist device placement is associated with an increase in cardiac MuRF1 expression. This prompted us to investigate the role of MuRF1 in two independent mouse models of cardiac atrophy: 1) cardiac hypertrophy regression after reversal of transaortic constriction (TAC) reversal and 2) dexamethasone-induced atrophy. Using echocardiographic, histological, and gene expression analyses, we found that upon TAC release, cardiac mass and cardiomyocyte cross-sectional areas in MuRF1(-/-) mice decreased approximately 70% less than in wild type mice in the 4 wk after release. This was in striking contrast to wild-type mice, who returned to baseline cardiac mass and cardiomyocyte size within 4 days of TAC release. Despite these differences in atrophic remodeling, the transcriptional activation of cardiac hypertrophy measured by beta-myosin heavy chain, smooth muscle actin, and brain natriuretic peptide was attenuated similarly in both MuRF1(-/-) and wild-type hearts after TAC release. In the second model, MuRF1(-/-) mice also displayed resistance to dexamethasone-induced cardiac atrophy, as determined by echocardiographic analysis. This study demonstrates, for the first time, that MuRF1 is essential for cardiac atrophy in vivo, both in the setting of therapeutic regression of cardiac hypertrophy and dexamethasone-induced atrophy.
