Document Detail


mTOR and vascular remodeling in lung diseases: current challenges and therapeutic prospects.
MedLine Citation:
PMID:  23355268     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Elena A Goncharova
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2013-01-25
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  27     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-01     Completed Date:  2013-07-01     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1796-807     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Anoxia / complications,  physiopathology
Apoptosis / physiology
Autophagy / physiology
Calcium Channels / physiology
Cell Proliferation / drug effects
Humans
Hypertension, Pulmonary / physiopathology*
Intercellular Signaling Peptides and Proteins / physiology
Lung / blood supply*
Multiprotein Complexes / physiology
Muscle, Smooth, Vascular / cytology
Pulmonary Artery / physiopathology
Pulmonary Circulation
Signal Transduction
Sirolimus / pharmacology
TOR Serine-Threonine Kinases / antagonists & inhibitors,  physiology*
Vascular Diseases / physiopathology
Grant Support
ID/Acronym/Agency:
1R01HL113178/HL/NHLBI NIH HHS; R01 HL113178/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Calcium Channels; 0/Intercellular Signaling Peptides and Proteins; 0/Multiprotein Complexes; 0/TOR complex 2; 0/mechanistic target of rapamycin complex 1; EC 2.7.1.1/MTOR protein, human; EC 2.7.1.1/TOR Serine-Threonine Kinases; W36ZG6FT64/Sirolimus
Comments/Corrections

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