PMID- 33512477
OWN - NLM
STAT- MEDLINE
DCOM- 20220301
LR  - 20220322
IS  - 1755-3245 (Electronic)
IS  - 0008-6363 (Print)
IS  - 0008-6363 (Linking)
VI  - 118
IP  - 2
DP  - 2022 Jan 29
TI  - The complex network of mTOR signalling in the heart.
PG  - 424-439
LID - 10.1093/cvr/cvab033 [doi]
AB  - 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.
CI  - Published on behalf of the European Society of Cardiology. All rights reserved. (c) 
      The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.
FAU - Sciarretta, Sebastiano
AU  - Sciarretta S
AD  - Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University 
      of Rome, Corso della Repubblica 79, 04100 Latina, Italy.
AD  - IRCCS Neuromed Pozzilli, Via Atinense, 18, 86077 Pozzilli Italy.
FAU - Forte, Maurizio
AU  - Forte M
AD  - IRCCS Neuromed Pozzilli, Via Atinense, 18, 86077 Pozzilli Italy.
FAU - Frati, Giacomo
AU  - Frati G
AD  - Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University 
      of Rome, Corso della Repubblica 79, 04100 Latina, Italy.
AD  - IRCCS Neuromed Pozzilli, Via Atinense, 18, 86077 Pozzilli Italy.
FAU - Sadoshima, Junichi
AU  - Sadoshima J
AUID- ORCID: 0000-0003-3724-4132
AD  - Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical 
      School, Cardiovascular Research Institute, 185 South Orange Avenue, G-609, 
      Newark, NJ 07103, USA.
LA  - eng
GR  - R01 HL067724/HL/NHLBI NIH HHS/United States
GR  - R01 HL091469/HL/NHLBI NIH HHS/United States
GR  - R01 HL138720/HL/NHLBI NIH HHS/United States
GR  - R01 HL112330/HL/NHLBI NIH HHS/United States
GR  - R01 HL144626/HL/NHLBI NIH HHS/United States
GR  - R01 HL150881/HL/NHLBI NIH HHS/United States
GR  - R01 AG023039/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (MTOR Inhibitors)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Heart Diseases/diagnosis/drug therapy/*enzymology/physiopathology
MH  - Humans
MH  - MTOR Inhibitors/therapeutic use
MH  - Mechanistic Target of Rapamycin Complex 1/*metabolism
MH  - Mechanistic Target of Rapamycin Complex 2/*metabolism
MH  - Myocytes, Cardiac/drug effects/*enzymology/pathology
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*metabolism
MH  - Translational Research, Biomedical
PMC - PMC8932297
OTO - NOTNLM
OT  - Heart disease
OT  - Rapamycin
OT  - mTOR
OT  - mTORC1
OT  - mTORC2
EDAT- 2021/01/30 06:00
MHDA- 2022/03/03 06:00
PMCR- 2021/01/29
CRDT- 2021/01/29 12:13
PHST- 2020/09/04 00:00 [received]
PHST- 2020/12/13 00:00 [revised]
PHST- 2021/01/26 00:00 [accepted]
PHST- 2021/01/30 06:00 [pubmed]
PHST- 2022/03/03 06:00 [medline]
PHST- 2021/01/29 12:13 [entrez]
PHST- 2021/01/29 00:00 [pmc-release]
AID - 6123788 [pii]
AID - cvab033 [pii]
AID - 10.1093/cvr/cvab033 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2022 Jan 29;118(2):424-439. doi: 10.1093/cvr/cvab033.