C/EBPβ Controls Exercise-Induced Cardiac Growth and Protects against Pathological Cardiac Remodeling
Open accessAbstract
The heart has the ability to grow in size in response to exercise, but little is known about the transcriptional mechanisms underlying physiological hypertrophy. Adult cardiomyocytes have also recently been proven to hold the potential for proliferation, a process that could be of great importance for regenerative medicine. Using a unique RT-PCR-based screen against all transcriptional components, we showed that C/EBPβ was downregulated with exercise, whereas the expression of CITED4 was increased. Reduction of C/EBPβ in vitro and in vivo resulted in a phenocopy of endurance exercise with cardiomyocyte hypertrophy and proliferation. This proliferation was mediated, at least in part, by the increased CITED4. Importantly, mice with reduced cardiac C/EBPβ levels displayed substantial resistance to cardiac failure upon pressure overload. These data indicate that C/EBPβ represses cardiomyocyte growth and proliferation in the adult mammalian heart and that reduction in C/EBPβ is a central signal in physiologic hypertrophy and proliferation.
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Another response of the heart to endurance exercise is limited proliferation of cardiomyocytes and cardiac stem cells in rodents.
“Another response of the heart to endurance exercise is the limited proliferation of cardiomyocytes and cardiac stem cells in rodents (16, 80, 146).”
From The Hippo signal transduction network for exercise physiologists (2016) · cites this paper as [16]
The Results section (“Cardiac hypertrophy and cardiomyocyte proliferation are induced following endurance exercise”; page unavailable) reports a small but significant increase in proliferation markers in cardiomyocytes of exercised mice and evidence of completed cell division. The passages do not establish that cardiac stem cells also proliferated in response to exercise, so that part of the claim is unsupported by this source. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSwim endurance training for 2 weeks increased expression of proliferation markers in mouse cardiomyocytes.
“Moreover, swim endurance training for 2 weeks increased the expression of proliferation markers in mouse cardiomyocytes (16),”
From The Hippo signal transduction network for exercise physiologists (2016) · cites this paper as [16]
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- Authors
- Boström, P., Mann, N., Wu, J., Quintero, P. A., Plovie, E. R., Panáková, D., Gupta, R. K., Xiao, C., MacRae, C. A., Rosenzweig, A., & Spiegelman, B. M.
- Affiliations
- Harvard University (US)
- Beth Israel Deaconess Medical Center (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Rosenzweig, Anthony
- Spiegelman, Bruce M.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 143
- Issue
- 7
- Pages
- 1072-1083
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3035164
- OpenAlex
- W2159745709
- Cited by
- 411
- References
- 27
- Citations by year
- 2026: 18 · 2025: 29 · 2024: 14 · 2023: 22 · 2022: 37 · 2021: 26 · 2020: 28 · 2019: 34 · 2018: 24 · 2017: 37 · 2016: 19 · 2015: 31 · 2014: 24 · 2013: 23 · 2012: 28
- FWCI
- 8.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- American Heart Association
- Wenner-Gren Foundation
- Hjärt-Lungfonden
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL085593, R01HL109264, K08HL076361)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK054477)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Effects of Exercise
- Keywords
- C/EBPβ, exercise-induced cardiac hypertrophy, cardiomyocyte proliferation, cardiac regeneration, heart failure, pressure overload, cardiac remodeling, transcriptional repression, endurance exercise, cardiomyocyte growth
- MeSH terms
- Animals, Cells, Cultured, Embryo, Nonmammalian, Gene Expression Regulation, Heart, Mice, Inbred C57BL, Myocardium, Physical Conditioning, Animal, Transcription Factors, Zebrafish, CCAAT-Enhancer-Binding Protein-beta, Myocytes, Cardiac, Cell Proliferation, Mice, Rats
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