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Updated: Feb 9, 2026
O-Ring Aortic Banding Versus Traditional Transverse Aortic Constriction for Modeling Pressure Overload-Induced Cardiac Hypertrophy
Published on: October 6, 2022
Extracellular signal-regulated kinase (ERK) activation preserves cardiac function in pressure overload induced
Michael Mutlak1, Michal Schlesinger-Laufer2, Tali Haas2
1The Rappaport Institute and the Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 31096, Israel.
Insights
The extracellular signal-regulated kinase (ERK) pathway promotes compensated cardiac hypertrophy, enhancing heart function and reducing fibrosis. Activating ERK may protect against pressure overload, but caution is advised with its inhibition in cancer therapy.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Signal Transduction
Background:
- Chronic pressure overload induces cardiac hypertrophy, potentially leading to heart failure.
- Extracellular signal-regulated kinase (ERK) activation is observed in hypertrophy but its role is debated.
Purpose of the Study:
- To investigate the role of activated extracellular signal-regulated kinase 1 (ERK1) in cardiac hypertrophy and pressure overload.
- To determine if ERK1 activation influences myocardial function and fibrosis.
Main Methods:
- Generated transgenic mice with cardiomyocyte-restricted overexpression of active ERK1.
- Studied hypertrophy and pressure-overload models in these mice.
Main Results:
- Activated ERK1 induced modest adaptive hypertrophy with improved contractile function and no fibrosis.
- In pressure-overload models, ERK1 activation reduced fibrosis and maintained ventricular function without increasing hypertrophy.
Conclusions:
- The ERK pathway promotes compensated cardiac hypertrophy, enhancing contractility and reducing fibrosis.
- ERK activation may be a therapeutic target for preserving heart function during pressure overload.
- Caution is recommended when inhibiting ERK in pressure-overload conditions due to potential adverse effects.
Background:
Chronic pressure overload and a variety of mediators induce concentric cardiac hypertrophy. When prolonged, cardiac hypertrophy culminates in decreased myocardial function and heart failure. Activation of the extracellular signal-regulated kinase (ERK) is consistently observed in animal models of hypertrophy and in human patients, but its role in the process is controversial.
Methods:
We generated transgenic mouse lines with cardiomyocyte restricted overexpression of intrinsically active ERK1, which similar to the observations in hypertrophy is phosphorylated on both the TEY and the Thr207 motifs and is overexpressed at pathophysiological levels.
Results:
The activated ERK1 transgenic mice developed a modest adaptive hypertrophy with increased contractile function and without fibrosis. Following induction of pressure-overload, where multiple pathways are stimulated, this activation did not further increase the degree of hypertrophy but protected the heart through a decrease in the degree of fibrosis and maintenance of ventricular contractile function.
Conclusions:
The ERK pathway acts to promote a compensated hypertrophic response, with enhanced contractile function and reduced fibrosis. The activation of this pathway may be a therapeutic strategy to preserve contractile function when the pressure overload cannot be easily alleviated. The inhibition of this pathway, which is increasingly being used for cancer therapy on the other hand, should be used with caution in the presence of pressure-overload.
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