Molecular basis of physiological heart growth: fundamental concepts and new players

M Maillet, JH Van Berlo, JD Molkentin - Nature reviews Molecular cell …, 2013 - nature.com
Nature reviews Molecular cell biology, 2013nature.com
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 …
Abstract
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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