New Insights Into the Role of mTOR Signaling in the Cardiovascular System.

Abstract:

:The mTOR (mechanistic target of rapamycin) is a master regulator of several crucial cellular processes, including protein synthesis, cellular growth, proliferation, autophagy, lysosomal function, and cell metabolism. mTOR interacts with specific adaptor proteins to form 2 multiprotein complexes, called mTORC1 (mTOR complex 1) and mTORC2 (mTOR complex 2). In the cardiovascular system, the mTOR pathway regulates both physiological and pathological processes in the heart. It is needed for embryonic cardiovascular development and for maintaining cardiac homeostasis in postnatal life. Studies involving mTOR loss-of-function models revealed that mTORC1 activation is indispensable for the development of adaptive cardiac hypertrophy in response to mechanical overload. mTORC2 is also required for normal cardiac physiology and ensures cardiomyocyte survival in response to pressure overload. However, partial genetic or pharmacological inhibition of mTORC1 reduces cardiac remodeling and heart failure in response to pressure overload and chronic myocardial infarction. In addition, mTORC1 blockade reduces cardiac derangements induced by genetic and metabolic disorders and has been reported to extend life span in mice. These studies suggest that pharmacological targeting of mTOR may represent a therapeutic strategy to confer cardioprotection, although clinical evidence in support of this notion is still scarce. This review summarizes and discusses the new evidence on the pathophysiological role of mTOR signaling in the cardiovascular system.

journal_name

Circ Res

journal_title

Circulation research

authors

Sciarretta S,Forte M,Frati G,Sadoshima J

doi

10.1161/CIRCRESAHA.117.311147

subject

Has Abstract

pub_date

2018-02-02 00:00:00

pages

489-505

issue

3

eissn

0009-7330

issn

1524-4571

pii

CIRCRESAHA.117.311147

journal_volume

122

pub_type

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