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Published on: June 29, 2014
Mechanisms of physiological and pathological cardiac hypertrophy
Michinari Nakamura1, Junichi Sadoshima2
1Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, NJ, USA.
Insights
Cardiac hypertrophy, an increase in heart muscle size, occurs in two forms: physiological and pathological. This review explores their molecular mechanisms, focusing on metabolic remodeling and therapeutic strategies for heart failure.
Area of Science:
- Cardiology
- Molecular Biology
- Physiology
Background:
- Cardiomyocytes in adult hearts do not divide, leading to size increase (hypertrophy) instead of number increase under stress.
- Cardiac hypertrophy is an adaptive response to workload, but pathological forms can lead to heart failure.
- Distinct signaling pathways regulate physiological and pathological cardiac hypertrophy.
Purpose of the Study:
- To review the molecular mechanisms of physiological and pathological cardiac hypertrophy.
- To emphasize the role of metabolic remodeling in cardiac hypertrophy.
- To discuss therapeutic strategies for preventing or reversing pathological hypertrophy.
Main Methods:
- Literature review of studies on cardiac hypertrophy mechanisms.
- Analysis of cellular signaling pathways involved in hypertrophy.
- Focus on metabolic, proliferative, and epigenetic regulatory mechanisms.
Main Results:
- Cardiac hypertrophy involves complex molecular pathways, including metabolism, non-coding RNAs, and epigenetic modifications.
- Metabolic remodeling is a key factor in both physiological and pathological cardiac hypertrophy.
- Understanding these mechanisms offers potential for novel therapeutic interventions.
Conclusions:
- Cardiac hypertrophy is regulated by diverse molecular mechanisms, with metabolic remodeling playing a crucial role.
- Targeting these pathways, particularly metabolic alterations, may lead to new treatments for heart failure.
- Further research into unrecognized mechanisms can advance therapeutic strategies for cardiac hypertrophy.
Abstract:
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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