| Follistatin-like 1 is an Akt-regulated cardioprotective factor that is secreted by the heart. | |
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MedLine Citation:
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PMID: 18519848 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The Akt protein kinase is an important mediator of cardiac myocyte growth and survival. To identify factors with novel therapeutic applications in cardiac diseases, we focused on the identification of factors secreted from Akt1-activated cells that have cardioprotective effects through autocrine/paracrine mechanisms. METHODS AND RESULTS: Using an inducible Akt1 transgenic mouse model, we have found that follistatin-like 1 (Fstl1) protein and transcript expression are increased 4.0- and 2.0-fold, respectively, by Akt activation in the heart (P<0.05). Fstl1 transcript was also upregulated in response to myocardial stresses including transverse aortic constriction, ischemia/reperfusion injury, and myocardial infarction. Adenovirus-mediated overexpression of Fstl1 protected cultured neonatal rat ventricular myocytes from hypoxia/reoxygenation-induced apoptosis (P<0.01), and this protective effect was dependent on the upregulation of both Akt and ERK activities. Conversely, knockdown of Fstl1 in cardiac myocytes decreased basal Akt signaling and increased the frequency of apoptotic death in vitro (P<0.01). The intravenous administration of an adenoviral encoding Fstl1 to mice resulted in a 66.0% reduction in myocardial infarct size after ischemia/reperfusion injury that was accompanied by a 70.9% reduction in apoptosis in the heart (P<0.01). CONCLUSIONS: These results indicate that Fstl1 is a cardiac-secreted factor that functions as an antiapoptotic protein. Fstl1 could play a role in myocardial maintenance and repair in response to harmful stimuli. |
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Authors:
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Yuichi Oshima; Noriyuki Ouchi; Kaori Sato; Yasuhiro Izumiya; David R Pimentel; Kenneth Walsh |
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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: 2008-06-02 |
Journal Detail:
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Title: Circulation Volume: 117 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2008 Jun |
Date Detail:
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Created Date: 2008-06-18 Completed Date: 2008-08-01 Revised Date: 2012-06-22 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
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Languages: eng Pagination: 3099-108 Citation Subset: AIM; IM |
Affiliation:
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Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University Medical School, 700 Albany St, W611, Boston, MA 02118, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cardiotonic Agents* Cloning, Molecular DNA, Complementary / genetics Follistatin-Related Proteins / genetics*, metabolism Gene Expression Regulation Heart / physiology* Humans Major Histocompatibility Complex / genetics Mice Mice, Transgenic Myocytes, Cardiac / physiology Oligonucleotide Array Sequence Analysis Proto-Oncogene Proteins c-akt / physiology* RNA, Small Interfering / genetics Rats Reperfusion Injury / genetics Transcription, Genetic Up-Regulation |
| Grant Support | |
ID/Acronym/Agency:
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AG15052/AG/NIA NIH HHS; HL71563/HL/NHLBI NIH HHS; HL77774/HL/NHLBI NIH HHS; HL81587/HL/NHLBI NIH HHS; HL86785/HL/NHLBI NIH HHS; P01 HL081587-04/HL/NHLBI NIH HHS; R01 AG015052-05/AG/NIA NIH HHS; R01 HL077774-04/HL/NHLBI NIH HHS; R01 HL086785-18/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cardiotonic Agents; 0/DNA, Complementary; 0/Follistatin-Related Proteins; 0/Fstl1 protein, mouse; 0/RNA, Small Interfering; 158709-62-7/Fstl1 protein, rat; EC 2.7.11.1/AKT1 protein, human; EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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