Molecular Mechanisms of Cardiac Remodeling and Regeneration in Physical Exercise
Open accessAbstract
Regular physical activity with aerobic and muscle-strengthening training protects against the occurrence and progression of cardiovascular disease and can improve cardiac function in heart failure patients. In the past decade significant advances have been made in identifying mechanisms of cardiomyocyte re-programming and renewal including an enhanced exercise-induced proliferational capacity of cardiomyocytes and its progenitor cells. Various intracellular mechanisms mediating these positive effects on cardiac function have been found in animal models of exercise and will be highlighted in this review. 1) activation of extracellular and intracellular signaling pathways including phosphatidylinositol 3 phosphate kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), EGFR/JNK/SP-1, nitric oxide (NO)-signaling, and extracellular vesicles; 2) gene expression modulation via microRNAs (miR), in particular via miR-17-3p and miR-222; and 3) modulation of cardiac cellular metabolism and mitochondrial adaption. Understanding the cellular mechanisms, which generate an exercise-induced cardioprotective cellular phenotype with physiological hypertrophy and enhanced proliferational capacity may give rise to novel therapeutic targets. These may open up innovative strategies to preserve cardiac function after myocardial injury as well as in aged cardiac tissue.
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During anabolic phase, activation of mTOR-dependent pathways supports protein synthesis and muscle remodeling.
“During the anabolic phase, the activation of the mechanistic target of rapamycin (mTOR)-dependent pathways supports protein synthesis and muscle remodeling [17].”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [17]
Section 2.3.1 (page unavailable) links exercise-associated Akt/mTOR activation to protein biosynthesis and physiological cardiac hypertrophy. It does not identify an anabolic phase or establish the claim for muscle remodeling generally rather than cardiac remodeling. (LLM, conf=0.86)
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Tero-Vescan, A., Degens, H., Matsakas, A., Ștefănescu, R., Ősz, B. E., & Slevin, M. (2025) · Pharmaceuticals · doi:10.3390/ph18081222 · Cited by 44 · see citing works
“During the anabolic phase, the activation of the mechanistic target of rapamycin (mTOR)-dependent pathways supports protein synthesis and muscle remodeling [17].”
The Catabolic—Anabolic Cycling Hormesis Model of Health and Resilience
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- Authors
- Schüttler, D., Clauss, S., Weckbach, L. T., & Brunner, S.
- Affiliations
- LMU Klinikum (DE)
- Corresponding author
- Brunner, Stefan
- Venue
- Cells
- Publisher
- MDPI AG
- Published
- 2019-09-23
- Volume
- 8
- Issue
- 10
- Pages
- 1128
- ISSN
- 2073-4409 (ISSN-L)
- PMC
- PMC6829258
- OpenAlex
- W2974286391
- Cited by
- 117
- References
- 137
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 16 · 2023: 20 · 2022: 32 · 2021: 23 · 2020: 7 · 2019: 1
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Cells (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Effects of Exercise
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- cardiac remodeling, cardiac regeneration, exercise training, cardiomyocyte proliferation, cardiac progenitor cells, PI3K/AKT/mTOR pathway, nitric oxide signaling, extracellular vesicles, microRNA, miR-17-3p, miR-222, myocardial metabolism, mitochondrial adaptation, cardiac hypertrophy, heart failure, myocardial injury, aging heart
- MeSH terms
- Animals, Heart, Humans, Regeneration, Signal Transduction, Exercise, Ventricular Remodeling, Myocytes, Cardiac
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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