Document Detail

Cardiac mTOR protects the heart against ischemia-reperfusion injury.
MedLine Citation:
PMID:  22561297     Owner:  NLM     Status:  MEDLINE    
Cardiac mammalian target of rapamycin (mTOR) is necessary and sufficient to prevent cardiac dysfunction in pathological hypertrophy. However, the role of cardiac mTOR in heart failure after ischemic injury remains undefined. To address this question, we used transgenic (Tg) mice with cardiac-specific overexpression of mTOR (mTOR-Tg mice) to study ischemia-reperfusion (I/R) injury in two animal models: 1) in vivo I/R injury with transient coronary artery ligation and 2) ex vivo I/R injury in Langendorff-perfused hearts with transient global ischemia. At 28 days after I/R, mortality was lower in mTOR-Tg mice than littermate control mice [wild-type (WT) mice]. Echocardiography and MRI demonstrated that global cardiac function in mTOR-Tg mice was preserved, whereas WT mice exhibited significant cardiac dysfunction. Masson's trichrome staining showed that 28 days after I/R, the area of interstitial fibrosis was smaller in mTOR-Tg mice compared with WT mice, suggesting that adverse left ventricular remodeling is inhibited in mTOR-Tg mice. In the ex vivo I/R model, mTOR-Tg hearts demonstrated improved functional recovery compared with WT hearts. Perfusion with Evans blue after ex vivo I/R yielded less staining in mTOR-Tg hearts than WT hearts, indicating that mTOR overexpression inhibited necrosis during I/R injury. Expression of proinflammatory cytokines, including IL-6 and TNF-α, in mTOR-Tg hearts was lower than in WT hearts. Consistent with this, IL-6 in the effluent post-I/R injury was lower in mTOR-Tg hearts than in WT hearts. These findings suggest that cardiac mTOR overexpression in the heart is sufficient to provide substantial cardioprotection against I/R injury and suppress the inflammatory response.
Toshinori Aoyagi; Yoichiro Kusakari; Chun-Yang Xiao; Brendan T Inouye; Masaya Takahashi; Marielle Scherrer-Crosbie; Anthony Rosenzweig; Kenta Hara; Takashi Matsui
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-04
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  303     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-03     Completed Date:  2012-09-04     Revised Date:  2013-07-02    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H75-85     Citation Subset:  IM    
Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, 96813, USA.
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MeSH Terms
Blotting, Western
Coronary Vessels / physiology
DNA / genetics,  isolation & purification
Inflammation / genetics,  pathology
Magnetic Resonance Imaging
Mice, Transgenic
Myocardial Ischemia / physiopathology
Myocardial Reperfusion Injury / pathology,  prevention & control*,  ultrasonography
Myocardium / pathology
Myocytes, Cardiac / pathology
Real-Time Polymerase Chain Reaction
TOR Serine-Threonine Kinases / genetics,  physiology*
Grant Support
Reg. No./Substance:
9007-49-2/DNA; EC Serine-Threonine Kinases; EC protein, mouse

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