ERK: A Key Player in the Pathophysiology of Cardiac Hypertrophy

Cardiac hypertrophy is an adaptive and compensatory mechanism preserving cardiac output during detrimental stimuli. Nevertheless, long-term stimuli incite chronic hypertrophy and may lead to heart failure. In this review, we analyze the recent literature regarding the role of ERK (extracellular sign...

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Bibliographic Details
Published in:International journal of molecular sciences 2019-05, Vol.20 (9), p.2164
Main Authors: Gallo, Simona, Vitacolonna, Annapia, Bonzano, Alessandro, Comoglio, Paolo, Crepaldi, Tiziana
Format: Article
Language:English
Subjects:
adaptive and maladaptive hypertrophy
anthracycline-induced cardiotoxicity
Apoptosis
Cardiomyocytes
Cardiomyopathy
Cardiovascular diseases
Cell cycle
Cell death
Congestive heart failure
Contraction
Coronary artery disease
Cytoplasm
Cytoskeleton
Dilated cardiomyopathy
ERK pathway
Extracellular signal-regulated kinase
Gene expression
Heart failure
Hypertension
hypertrophic cardiomyopathy
Hypertrophy
Kinases
Myocardial infarction
Phosphorylation
Physiology
Proteins
RASopathies
Regulators
Review
target therapies
Toxicity
Transgenic animals
Workloads
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Summary:Cardiac hypertrophy is an adaptive and compensatory mechanism preserving cardiac output during detrimental stimuli. Nevertheless, long-term stimuli incite chronic hypertrophy and may lead to heart failure. In this review, we analyze the recent literature regarding the role of ERK (extracellular signal-regulated kinase) activity in cardiac hypertrophy. ERK signaling produces beneficial effects during the early phase of chronic pressure overload in response to G protein-coupled receptors (GPCRs) and integrin stimulation. These functions comprise (i) adaptive concentric hypertrophy and (ii) cell death prevention. On the other hand, ERK participates in maladaptive hypertrophy during hypertension and chemotherapy-mediated cardiac side effects. Specific ERK-associated scaffold proteins are implicated in either cardioprotective or detrimental hypertrophic functions. Interestingly, ERK phosphorylated at threonine 188 and activated ERK5 (the big MAPK 1) are associated with pathological forms of hypertrophy. Finally, we examine the connection between ERK activation and hypertrophy in (i) transgenic mice overexpressing constitutively activated RTKs (receptor tyrosine kinases), (ii) animal models with mutated sarcomeric proteins characteristic of inherited hypertrophic cardiomyopathies (HCMs), and (iii) mice reproducing syndromic genetic RASopathies. Overall, the scientific literature suggests that during cardiac hypertrophy, ERK could be a "good" player to be stimulated or a "bad" actor to be mitigated, depending on the pathophysiological context.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms20092164