Molecular basis of physiological heart growth: fundamental concepts and new players
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The heart hypertrophies in response to developmental signals as well as increased workload. Although adult-onset hypertrophy can ultimately lead to disease, cardiac hypertrophy is not necessarily maladaptive and can even be beneficial. Progress has been made in our understanding of the structural and molecular characteristics of physiological cardiac hypertrophy, as well as of the endocrine effectors and associated signalling pathways that regulate it. Physiological hypertrophy is initiated by finite signals, which include growth hormones (such as thyroid hormone, insulin, insulin-like growth factor 1 and vascular endothelial growth factor) and mechanical forces that converge on a limited number of intracellular signalling pathways (such as PI3K, AKT, AMP-activated protein kinase and mTOR) to affect gene transcription, protein translation and metabolism. Harnessing adaptive signalling mediators to reinvigorate the diseased heart could have important medical ramifications.
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Adult cardiomyocytes have an aspect ratio of 7:1 to 9.5:1, while heterogeneous hiPSC-CMs are smaller with aspect ratios of 2-3:1.
“rod-like adult CMs have an aspect ratio between 7:1 to 9.5:1 [164], heterogeneous hiPSC-CMs are much smaller with lower aspect ratios (2–3:1) [165,166].”
From Cardiovascular disease models: A game changing paradigm in drug discovery and screening (2019) · cites this paper as [165]
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- Authors
- Maillet, M., van Berlo, J. H., & Molkentin, J. D.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- Corresponding author
- Molkentin, Jeffery D.
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2012-12-21
- Volume
- 14
- Issue
- 1
- Pages
- 38-48
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- PMC
- PMC4416212
- OpenAlex
- W2045575123
- Cited by
- 536
- References
- 128
- Citations by year
- 2026: 16 · 2025: 29 · 2024: 30 · 2023: 34 · 2022: 32 · 2021: 56 · 2020: 46 · 2019: 49 · 2018: 37 · 2017: 50 · 2016: 41 · 2015: 53 · 2014: 41 · 2013: 20 · 2012: 1
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Heart, Lung, and Blood Institute (R00HL112852)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- physiological cardiac hypertrophy, cardiac growth, thyroid hormones, insulin, insulin-like growth factor I, vascular endothelial growth factor, mechanical loading, PI3K/Akt signaling, AMPK, mTOR signaling, heart development, myocardial metabolism, gene transcription, mRNA translation
- MeSH terms
- Animals, Energy Metabolism, Heart, Cardiomegaly, Heart Failure, Humans, Thyroid Hormones, Transcription, Genetic, Protein Biosynthesis, Signal Transduction, Mice
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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