| Cardiac mTOR protects the heart against ischemia-reperfusion injury. | |
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MedLine Citation:
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PMID: 22561297 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-05-04 |
Journal Detail:
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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:
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Created Date: 2012-07-03 Completed Date: 2012-09-04 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H75-85 Citation Subset: IM |
Affiliation:
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Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, 96813, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Autophagy Blotting, Western Coronary Vessels / physiology DNA / genetics, isolation & purification Fibrosis Inflammation / genetics, pathology Ligation Magnetic Resonance Imaging Male Mice Mice, Transgenic Myocardial Ischemia / physiopathology Myocardial Reperfusion Injury / pathology, prevention & control*, ultrasonography Myocardium / pathology Myocytes, Cardiac / pathology Necrosis Perfusion Real-Time Polymerase Chain Reaction TOR Serine-Threonine Kinases / genetics, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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HL-094677/HL/NHLBI NIH HHS; HL-098423/HL/NHLBI NIH HHS; R01 HL098423/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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9007-49-2/DNA; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.1.1/mTOR protein, mouse |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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