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Cytoplasmic signaling pathways that regulate cardiac hypertrophy
1Department of Pediatrics, Division of Molecular Cardiovascular Biology, Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229-3039, USA. jeff.molkentin@chmcc.org
Insights
Cardiac hypertrophy, an adaptive response, can lead to heart failure. This review explores the complex signaling pathways that regulate cardiomyocyte growth, highlighting their role in disease progression.
Area of Science:
- Cardiology
- Molecular Biology
- Cell Signaling
Background:
- Cardiac hypertrophy is an adaptive response of cardiomyocytes to stress.
- Sustained cardiac hypertrophy is a major risk factor for heart failure.
Purpose of the Study:
- To review the current understanding of cardiomyocyte signal transduction.
- To discuss the regulation of the hypertrophic response.
Main Methods:
- Literature review of signaling pathways involved in cardiac hypertrophy.
- Analysis of intracellular signaling cascades.
Main Results:
- Multiple signaling pathways, including G proteins, GTPases (Ras, RhoA, Rac), MAPK cascades, and others, are involved in hypertrophic response.
- These pathways function in concert to regulate cardiomyocyte hypertrophy.
Conclusions:
- Understanding these pathways is crucial for developing treatments for heart failure.
- A coordinated action of multiple signaling pathways orchestrates cardiac hypertrophy.
Abstract:
This review discusses the rapidly progressing field of cardiomyocyte signal transduction and the regulation of the hypertrophic response. When stimulated by a wide array of neurohumoral factors or when faced with an increase in ventricular-wall tension, individual cardiomyocytes undergo hypertrophic growth as an adaptive response. However, sustained cardiac hypertrophy is a leading predictor of future heart failure. A growing number of intracellular signaling pathways have been characterized as important transducers of the hypertrophic response, including specific G protein isoforms, low-molecular-weight GTPases (Ras, RhoA, and Rac), mitogen-activated protein kinase cascades, protein kinase C, calcineurin, gp130-signal transducer and activator of transcription, insulin-like growth factor I receptor pathway, fibroblast growth factor and transforming growth factor beta receptor pathways, and many others. Each of these signaling pathways has been implicated as a hypertrophic transducer, which collectively suggests an emerging paradigm whereby multiple pathways operate in concert to orchestrate a hypertrophic response