| Hypercholesterolemia is associated with hyperactive cardiac mTORC1 and mTORC2 signaling. | |
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MedLine Citation:
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PMID: 19395857 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Nutritional excess and hyperlipidemia increase the heart's susceptibility to ischemic injury. Mammalian target of rapamycin (mTOR) controls the cellular response to nutritional status and may play a role in ischemic injury. To explore the effect of hypercholesterolemia on cardiac mTOR signaling, we assessed mTOR signaling in hypercholesterolemic swine (HC) that are also susceptible to increased cardiac ischemia-reperfusion injury. Yucatan pigs were fed a high-fat/high-cholesterol diet for 4 weeks to induce hypercholesterolemia, and mTOR signaling was measured by immunoblotting and immunofluorescence in the non-ischemic left ventricular area. Total myocardial mTOR and raptor levels were markedly increased in the HC group compared to the normocholesterolemic group, and directly correlated with serum cholesterol levels. mTOR exhibited intense perinuclear staining in myocytes only in the HC group. Hypercholesterolemia was associated with hyperactive signaling upstream and downstream of both mTOR complexes, including myocardial Akt, S6K1, 4EBP1, S6 and PKC-alpha, increased levels of cardiac hypertrophy markers, and a trend toward lower levels of myocardial autophagy. Hypercholesterolemia can now be added to the growing list of conditions associated with aberrant mTOR signaling. Hypercholesterolemia produces a unique profile of alterations in cardiac mTOR signaling, which is a potential target in cardiac diseases associated with hypercholesterolemia and nutritional excess. |
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Authors:
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Hilary P Glazer; Robert M Osipov; Richard T Clements; Frank W Sellke; Cesario Bianchi |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-06-03 |
Journal Detail:
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Title: Cell cycle (Georgetown, Tex.) Volume: 8 ISSN: 1551-4005 ISO Abbreviation: Cell Cycle Publication Date: 2009 Jun |
Date Detail:
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Created Date: 2009-05-18 Completed Date: 2009-07-28 Revised Date: 2013-06-02 |
Medline Journal Info:
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Nlm Unique ID: 101137841 Medline TA: Cell Cycle Country: United States |
Other Details:
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Languages: eng Pagination: 1738-46 Citation Subset: IM |
Affiliation:
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Division of Cardiothoracic Surgery Research, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA 02215, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Dietary Fats / administration & dosage Eukaryotic Initiation Factors / metabolism Hypercholesterolemia / enzymology, metabolism* Male Myocytes, Cardiac / metabolism* Protein Kinase C-alpha / metabolism Protein Kinases / metabolism* Proto-Oncogene Proteins c-akt / metabolism Ribosomal Protein S6 / metabolism Ribosomal Protein S6 Kinases, 70-kDa / metabolism Signal Transduction Swine TOR Serine-Threonine Kinases Transcription Factors / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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HL076130/HL/NHLBI NIH HHS; HL46716/HL/NHLBI NIH HHS; HL69024/HL/NHLBI NIH HHS; R01 HL046716-08/HL/NHLBI NIH HHS; R01 HL069024-05/HL/NHLBI NIH HHS; R01 HL069024-09/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Dietary Fats; 0/Eukaryotic Initiation Factors; 0/Ribosomal Protein S6; 0/Transcription Factors; EC 2.7.-/Protein Kinases; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.1/Ribosomal Protein S6 Kinases, 70-kDa; EC 2.7.11.1/ribosomal protein S6 kinase, 70kD, polypeptide 1; EC 2.7.11.13/Protein Kinase C-alpha |
| Comments/Corrections | |
Comment In:
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Cell Cycle. 2009 Jun 1;8(11):1646
[PMID:
19454842
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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