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Extracellular signal-regulated kinase (ERK) activation preserves cardiac function in pressure overload induced hypertrophy
- Source :
- International Journal of Cardiology. 270:204-213
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- 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.
- Subjects :
- Male
0301 basic medicine
MAPK/ERK pathway
Cardiac function curve
MAP Kinase Signaling System
Blood Pressure
Cardiomegaly
Mice, Transgenic
030204 cardiovascular system & hematology
Muscle hypertrophy
Mice
03 medical and health sciences
0302 clinical medicine
Fibrosis
medicine
Animals
Myocytes, Cardiac
Rats, Wistar
Cells, Cultured
Pressure overload
Mitogen-Activated Protein Kinase 3
biology
business.industry
medicine.disease
Myocardial Contraction
Rats
Cell biology
Phospholamban
Enzyme Activation
030104 developmental biology
Animals, Newborn
Heart failure
Mitogen-activated protein kinase
biology.protein
Female
Cardiology and Cardiovascular Medicine
business
Subjects
Details
- ISSN :
- 01675273
- Volume :
- 270
- Database :
- OpenAIRE
- Journal :
- International Journal of Cardiology
- Accession number :
- edsair.doi.dedup.....d1b518755b960fa35f4b49fc221bfea8