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How to Steer and Control ERK and the ERK Signaling Cascade Exemplified by Looking at Cardiac Insufficiency
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MAPK/ERK Signaling in Regulation of Renal Differentiation
Review

ERK: A Key Player in the Pathophysiology of Cardiac Hypertrophy

1
Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo (TO), Italy
2
Department of Oncology, University of Turin, 10143 Orbassano (TO), Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(9), 2164; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20092164
Received: 22 March 2019 / Revised: 26 April 2019 / Accepted: 29 April 2019 / Published: 1 May 2019
(This article belongs to the Special Issue ERK Signaling Pathway in Diseases)
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. View Full-Text
Keywords: ERK pathway; adaptive and maladaptive hypertrophy; anthracycline-induced cardiotoxicity; hypertrophic cardiomyopathy; RASopathies; target therapies ERK pathway; adaptive and maladaptive hypertrophy; anthracycline-induced cardiotoxicity; hypertrophic cardiomyopathy; RASopathies; target therapies
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MDPI and ACS Style

Gallo, S.; Vitacolonna, A.; Bonzano, A.; Comoglio, P.; Crepaldi, T. ERK: A Key Player in the Pathophysiology of Cardiac Hypertrophy. Int. J. Mol. Sci. 2019, 20, 2164. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20092164

AMA Style

Gallo S, Vitacolonna A, Bonzano A, Comoglio P, Crepaldi T. ERK: A Key Player in the Pathophysiology of Cardiac Hypertrophy. International Journal of Molecular Sciences. 2019; 20(9):2164. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20092164

Chicago/Turabian Style

Gallo, Simona, Annapia Vitacolonna, Alessandro Bonzano, Paolo Comoglio, and Tiziana Crepaldi. 2019. "ERK: A Key Player in the Pathophysiology of Cardiac Hypertrophy" International Journal of Molecular Sciences 20, no. 9: 2164. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20092164

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