Met tyrosine kinase receptor, also known as c-Met, is the HGF (hepatocyte growth factor) receptor. The HGF/Met pathway has a prominent role in cardiovascular remodelling after tissue injury. The present review provides a synopsis of the cellular and molecular mechanisms underlying the effects of HGF/Met in the heart and blood vessels. In vivo, HGF/Met function is particularly important for the protection of the heart in response to both acute and chronic insults, including ischaemic injury and doxorubicin-induced cardiotoxicity. Accordingly, conditional deletion of Met in cardiomyocytes results in impaired organ defence against oxidative stress. After ischaemic injury, activation of Met provides strong anti-apoptotic stimuli for cardiomyocytes through PI3K (phosphoinositide 3-kinase)/Akt and MAPK (mitogen-activated protein kinase) cascades. Recently, we found that HGF/Met is also important for autophagy regulation in cardiomyocytes via the mTOR (mammalian target of rapamycin) pathway. HGF/Met induces proliferation and migration of endothelial cells through Rac1 (Ras-related C3 botulinum toxin substrate 1) activation. In fibroblasts, HGF/Met antagonizes the actions of TGFβ1 (transforming growth factor β1) and AngII (angiotensin II), thus preventing fibrosis. Moreover, HGF/Met influences the inflammatory response of macrophages and the immune response of dendritic cells, indicating its protective function against atherosclerotic and autoimmune diseases. The HGF/Met axis also plays an important role in regulating self-renewal and myocardial regeneration through the enhancement of cardiac progenitor cells. HGF/Met has beneficial effects against myocardial infarction and endothelial dysfunction: the cellular and molecular mechanisms underlying repair function in the heart and blood vessels are common and include pro-angiogenic, anti-inflammatory and anti-fibrotic actions. Thus administration of HGF or HGF mimetics may represent a promising therapeutic agent for the treatment of both coronary and peripheral artery disease.
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Review Article|
November 11 2015
Cellular and molecular mechanisms of HGF/Met in the cardiovascular system
Simona Gallo;
Simona Gallo
*Department of Oncology, University of Turin, Turin, Italy
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Valentina Sala;
Valentina Sala
*Department of Oncology, University of Turin, Turin, Italy
†Department of Medical Sciences, University of Turin, Turin, Italy
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Stefano Gatti;
Stefano Gatti
*Department of Oncology, University of Turin, Turin, Italy
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Tiziana Crepaldi
*Department of Oncology, University of Turin, Turin, Italy
Correspondence: Professor Tiziana Crepaldi (email tiziana.crepaldi@unito.it).
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Publisher: Portland Press Ltd
Received:
July 17 2015
Revision Received:
September 21 2015
Accepted:
September 30 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2015 Authors; published by Portland Press Limited
2015
Clin Sci (Lond) (2015) 129 (12): 1173–1193.
Article history
Received:
July 17 2015
Revision Received:
September 21 2015
Accepted:
September 30 2015
Citation
Simona Gallo, Valentina Sala, Stefano Gatti, Tiziana Crepaldi; Cellular and molecular mechanisms of HGF/Met in the cardiovascular system. Clin Sci (Lond) 1 December 2015; 129 (12): 1173–1193. doi: https://doi.org/10.1042/CS20150502
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