<p class="first" id="d1755531e69">Cardiomyocytes exit the cell cycle and become terminally
differentiated soon after
birth. Therefore, in the adult heart, instead of an increase in cardiomyocyte number,
individual cardiomyocytes increase in size, and the heart develops hypertrophy to
reduce ventricular wall stress and maintain function and efficiency in response to
an increased workload. There are two types of hypertrophy: physiological and pathological.
Hypertrophy initially develops as an adaptive response to physiological and pathological
stimuli, but pathological hypertrophy generally progresses to heart failure. Each
form of hypertrophy is regulated by distinct cellular signalling pathways. In the
past decade, a growing number of studies have suggested that previously unrecognized
mechanisms, including cellular metabolism, proliferation, non-coding RNAs, immune
responses, translational regulation, and epigenetic modifications, positively or negatively
regulate cardiac hypertrophy. In this Review, we summarize the underlying molecular
mechanisms of physiological and pathological hypertrophy, with a particular emphasis
on the role of metabolic remodelling in both forms of cardiac hypertrophy, and we
discuss how the current knowledge on cardiac hypertrophy can be applied to develop
novel therapeutic strategies to prevent or reverse pathological hypertrophy.
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