Physiological hypertrophy is an adaptive form of cardiac hypertrophy that does not lead to heart disease in healthy individuals.
This cardiac growth maintains or augments cardiac function and increases angiogenesis and metabolism. Physiological hypertrophy does not promote fibrotic remodelling or cardiomyocyte death.
Physiological hypertrophy is initiated by specific hormones (triiodothyronine, insulin, insulin-like growth factor 1 and vascular endothelial growth factor) or stretch (loading), which activate a restricted number of intracellular signalling pathways (PI3K, AKT, mTOR and ERK1/2).
Metabolic reprogramming governed by AMP-activated protein kinase (AMPK) is essential for adaptive cardiac hypertrophy.
Exercise induced hypertrophy causes a downregulation of CCAAT/enhancer binding protein-β and the transcription of an exercise-specific gene set.
Intermittent PI3K, AKT, ERK1/2 or AMPK activation promotes the activation of a physiological hypertrophic programme to maintain or augment function, thus antagonizing pathological conditions.
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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This work was supported by grants from the US National Institutes of Health (J.D.M., J.H.v.B. and M.M.), and the Howard Hughes Medical Institute (J.D.M).
The authors declare no competing financial interests.
From the Greek mys (muscle) and kardia (heart). It is the thick middle muscular layer of the heart that contracts.
- Valvular stenosis
Also called heart valve disease. Valvular stenosis occurs in response to stiffening, thickening, fusion or blockage of one or more valves of the heart. The heart comprises four valves: the mitral, aortic, tricuspid and pulmonic valves.
- Transverse-tubule system
Also called the T-tubule system. A T-tubule is a deep invagination of the sarcolemma (cardiomyocyte plasma membrane) enriched in excitation–contraction coupling molecules. T-tubule system refers to the network of T-tubules within an adult cardiomyocyte.
- Systolic function
The performance of the left ventricle during systole, which is the contraction of the heart. The best index of left ventricle systolic function is ejection fraction, which is calculated as the difference between end-diastolic and end-systolic left ventricle volume, divided by the end-diastolic left ventricle volume.
- Diastolic function
The performance of the left ventricle during diastole, which is the relaxation of the heart and the filling of the ventricle.
- Arrhythmogenic channelopathies
Genetic or acquired cardiac ion channel diseases. Ion channels (sodium, potassium and calcium channels) control the electrical activity of the heart. Abnormal electrical activity can lead to cardiac arrhythmias (irregular cardiac rhythm) and sudden death.
Inflammation of the heart caused by a viral or bacterial infection or an autoimmune disease. Myocarditis sometimes induces eccentric hypertrophy and heart failure.
- Stretch–spring sensing
Translation of changes in the cardiomyocyte extracellular environment (stretch) and the sarcomeres elasticity (spring) into biochemical hypertrophic signals.
Specialized plasma membrane of a myocyte.
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Maillet, M., van Berlo, J. & Molkentin, J. Molecular basis of physiological heart growth: fundamental concepts and new players. Nat Rev Mol Cell Biol 14, 38–48 (2013). https://doi.org/10.1038/nrm3495
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