PMID- 23355268
OWN - NLM
STAT- MEDLINE
DCOM- 20130701
LR  - 20211203
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 27
IP  - 5
DP  - 2013 May
TI  - mTOR and vascular remodeling in lung diseases: current challenges and therapeutic 
      prospects.
PG  - 1796-807
LID - 10.1096/fj.12-222224 [doi]
AB  - Mammalian target of rapamycin (mTOR) is a major regulator of cellular metabolism, 
      proliferation, and survival that is implicated in various proliferative and 
      metabolic diseases, including obesity, type 2 diabetes, hamartoma syndromes, and 
      cancer. Emerging evidence suggests a potential critical role of mTOR signaling in 
      pulmonary vascular remodeling. Remodeling of small pulmonary arteries due to 
      increased proliferation, resistance to apoptosis, and altered metabolism of cells 
      forming the pulmonary vascular wall is a key currently irreversible pathological 
      feature of pulmonary hypertension, a progressive pulmonary vascular disorder with 
      high morbidity and mortality. In addition to rare familial and idiopathic forms, 
      pulmonary hypertension is also a life-threatening complication of several lung 
      diseases associated with hypoxia. This review aims to summarize our current 
      knowledge and recent advances in understanding the role of the mTOR pathway in 
      pulmonary vascular remodeling, with a specific focus on the hypoxia component, a 
      confirmed shared trigger of pulmonary hypertension in lung diseases. We also 
      discuss the emerging role of mTOR as a promising therapeutic target and mTOR 
      inhibitors as potential pharmacological approaches to treat pulmonary vascular 
      remodeling in pulmonary hypertension.
FAU - Goncharova, Elena A
AU  - Goncharova EA
AD  - University of Pennsylvania Perelman School of Medicine, Translational Research 
      Laboratories, Rm. 1214, 125 South 31st St., Philadelphia, PA 19104, USA. 
      goncharo@mail.med.upenn.edu
LA  - eng
GR  - R01 HL113178/HL/NHLBI NIH HHS/United States
GR  - 1R01HL113178/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20130125
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Calcium Channels)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Multiprotein Complexes)
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)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Apoptosis/physiology
MH  - Autophagy/physiology
MH  - Calcium Channels/physiology
MH  - Cell Proliferation/drug effects
MH  - Humans
MH  - Hypertension, Pulmonary/*physiopathology
MH  - Hypoxia/complications/physiopathology
MH  - Intercellular Signaling Peptides and Proteins/physiology
MH  - Lung/*blood supply
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mechanistic Target of Rapamycin Complex 2
MH  - Multiprotein Complexes/physiology
MH  - Muscle, Smooth, Vascular/cytology
MH  - Pulmonary Artery/physiopathology
MH  - Pulmonary Circulation
MH  - Signal Transduction
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*physiology
MH  - Vascular Diseases/physiopathology
PMC - PMC3633815
EDAT- 2013/01/29 06:00
MHDA- 2013/07/03 06:00
PMCR- 2014/05/01
CRDT- 2013/01/29 06:00
PHST- 2013/01/29 06:00 [entrez]
PHST- 2013/01/29 06:00 [pubmed]
PHST- 2013/07/03 06:00 [medline]
PHST- 2014/05/01 00:00 [pmc-release]
AID - fj.12-222224 [pii]
AID - 12-222224 [pii]
AID - 10.1096/fj.12-222224 [doi]
PST - ppublish
SO  - FASEB J. 2013 May;27(5):1796-807. doi: 10.1096/fj.12-222224. Epub 2013 Jan 25.