The mechanistic target of rapamycin (mTOR) integrates several intracellular and extracellular signals involved in the regulation of anabolic and catabolic processes. mTOR assembles into two macromolecular complexes, named mTORC1 and mTORC2, which have different regulators, substrates and functions. Studies of gain- and loss-of-function animal models of mTOR signalling revealed that mTORC1/2 elicits both adaptive and maladaptive functions in the cardiovascular system. Both mTORC1 and mTORC2 are indispensable for driving cardiac development and cardiac adaption to stress, such as pressure overload. However, persistent and deregulated mTORC1 activation in the heart is detrimental during stress and contributes to the development and progression of cardiac remodelling and genetic and metabolic cardiomyopathies. In this review, we discuss the latest findings regarding the role of mTOR in the cardiovascular system, both under basal conditions and during stress, such as pressure overload, ischemia, and metabolic stress. Current data suggest that mTOR modulation may represent a potential therapeutic strategy for the treatment of cardiac diseases.

The complex network of mTOR signalling in the heart / Sciarretta, S.; Forte, M.; Frati, G.; Sadoshima, J.. - In: CARDIOVASCULAR RESEARCH. - ISSN 0008-6363. - 118:2(2022), pp. 424-439. [10.1093/cvr/cvab033]

The complex network of mTOR signalling in the heart

Sciarretta S.;Frati G.;
2022

Abstract

The mechanistic target of rapamycin (mTOR) integrates several intracellular and extracellular signals involved in the regulation of anabolic and catabolic processes. mTOR assembles into two macromolecular complexes, named mTORC1 and mTORC2, which have different regulators, substrates and functions. Studies of gain- and loss-of-function animal models of mTOR signalling revealed that mTORC1/2 elicits both adaptive and maladaptive functions in the cardiovascular system. Both mTORC1 and mTORC2 are indispensable for driving cardiac development and cardiac adaption to stress, such as pressure overload. However, persistent and deregulated mTORC1 activation in the heart is detrimental during stress and contributes to the development and progression of cardiac remodelling and genetic and metabolic cardiomyopathies. In this review, we discuss the latest findings regarding the role of mTOR in the cardiovascular system, both under basal conditions and during stress, such as pressure overload, ischemia, and metabolic stress. Current data suggest that mTOR modulation may represent a potential therapeutic strategy for the treatment of cardiac diseases.
2022
heart disease; mTOR; mTORC1; mTORC2; rapamycin
01 Pubblicazione su rivista::01a Articolo in rivista
The complex network of mTOR signalling in the heart / Sciarretta, S.; Forte, M.; Frati, G.; Sadoshima, J.. - In: CARDIOVASCULAR RESEARCH. - ISSN 0008-6363. - 118:2(2022), pp. 424-439. [10.1093/cvr/cvab033]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1687809
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