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Updated: Jan 10, 2026
Disorders of Erythrocytes
Signaling effectors underlying pathologic growth and remodeling of the heart
Jop H van Berlo1, Marjorie Maillet, Jeffery D Molkentin
1Department of Pediatrics, University of Cincinnati, Cincinnati Children’s Hospital Medical Center, Howard Hughes Medical Institute, Cincinnati, Ohio 45229-3039, USA.
Insights
Cardiac hypertrophy, an enlargement of heart muscle cells, is a major risk factor for heart failure. Emerging therapies target molecular pathways involved in this maladaptive cardiac remodeling for potential clinical trials.
Area of Science:
- Cardiology and cardiovascular research.
- Molecular and genetic basis of cardiovascular disease.
- Translational medicine and therapeutic development.
Background:
- Cardiovascular disease is the leading cause of death globally.
- Cardiac hypertrophy is an initial compensatory response to heart conditions, involving myocyte enlargement.
- Progressive hypertrophy becomes maladaptive, predicting heart failure, arrhythmia, and sudden death.
Purpose of the Study:
- To review therapeutic strategies for cardiovascular disease derived from molecular and genetic studies.
- To highlight emerging therapeutic targets for cardiac hypertrophy with translational potential.
- To discuss pharmacologic agents suitable for human clinical trials.
Main Methods:
- Review of molecular and genetic studies in animal models of cardiovascular disease.
- Analysis of intracellular signaling pathways implicated in cardiac remodeling and hypertrophy.
- Identification of therapeutic targets with potential for clinical translation.
Main Results:
- Intracellular signaling pathways are central to pathological cardiac remodeling and hypertrophy.
- Selected therapeutic targets show promise for intervention in cardiac hypertrophy.
- Available pharmacologic agents can be readily evaluated in clinical trials.
Conclusions:
- Targeting molecular pathways offers promising therapeutic avenues for cardiovascular disease.
- Emerging targets in cardiac hypertrophy have significant translational potential.
- Clinical evaluation of pharmacologic agents is feasible for treating maladaptive cardiac remodeling.
Abstract:
Cardiovascular disease is the number one cause of mortality in the Western world. The heart responds to many cardiopathological conditions with hypertrophic growth by enlarging individual myocytes to augment cardiac pump function and decrease ventricular wall tension. Initially, such cardiac hypertrophic growth is often compensatory, but as time progresses these changes become maladaptive. Cardiac hypertrophy is the strongest predictor for the development of heart failure, arrhythmia, and sudden death. Here we discuss therapeutic avenues emerging from molecular and genetic studies of cardiovascular disease in animal models. The majority of these are based on intracellular signaling pathways considered central to pathologic cardiac remodeling and hypertrophy, which then leads to heart failure. We focus our discussion on selected therapeutic targets that have more recently emerged and have a tangible translational potential given the available pharmacologic agents that could be readily evaluated in human clinical trials.
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