Document Detail

PI3K(p110 alpha) protects against myocardial infarction-induced heart failure: identification of PI3K-regulated miRNA and mRNA.
MedLine Citation:
PMID:  20237330     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Myocardial infarction (MI) is a serious complication of atherosclerosis associated with increasing mortality attributable to heart failure. Activation of phosphoinositide 3-kinase [PI3K(p110 alpha)] is considered a new strategy for the treatment of heart failure. However, whether PI3K(p110 alpha) provides protection in a setting of MI is unknown, and PI3K(p110 alpha) is difficult to target because it has multiple actions in numerous cell types. The goal of this study was to assess whether PI3K(p110 alpha) is beneficial in a setting of MI and, if so, to identify cardiac-selective microRNA and mRNA that mediate the protective properties of PI3K(p110 alpha). METHODS AND RESULTS: Cardiomyocyte-specific transgenic mice with increased or decreased PI3K(p110 alpha) activity (caPI3K-Tg and dnPI3K-Tg, respectively) were subjected to MI for 8 weeks. The caPI3K-Tg subjected to MI had better cardiac function than nontransgenic mice, whereas dnPI3K-Tg had worse function. Using microarray analysis, we identified PI3K-regulated miRNA and mRNA that were correlated with cardiac function, including growth factor receptor-bound 14. Growth factor receptor-bound 14 is highly expressed in the heart and positively correlated with PI3K(p110 alpha) activity and cardiac function. Mice deficient in growth factor receptor-bound 14 have cardiac dysfunction. CONCLUSIONS: Activation of PI3K(p110 alpha) protects the heart against MI-induced heart failure. Cardiac-selective targets that mediate the protective effects of PI3K(p110 alpha) represent new drug targets for heart failure.
Ruby C Y Lin; Kate L Weeks; Xiao-Ming Gao; Rohan B H Williams; Bianca C Bernardo; Helen Kiriazis; Vance B Matthews; Elizabeth A Woodcock; Russell D Bouwman; Janelle P Mollica; Helen J Speirs; Ian W Dawes; Roger J Daly; Tetsuo Shioi; Seigo Izumo; Mark A Febbraio; Xiao-Jun Du; Julie R McMullen
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  30     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-18     Completed Date:  2010-04-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  724-32     Citation Subset:  IM    
Ramaciotti Centre for Gene Function Analysis, University of New South Wales, Randwick, Australia.
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MeSH Terms
1-Phosphatidylinositol 3-Kinase / genetics,  metabolism*
Disease Models, Animal
Gene Expression Profiling / methods
Heart Failure / enzymology,  genetics,  physiopathology,  prevention & control*,  ultrasonography
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
MicroRNAs / metabolism*
Myocardial Infarction / complications,  enzymology*,  genetics,  physiopathology,  ultrasonography
Myocardium / enzymology*,  pathology
Oligonucleotide Array Sequence Analysis
Proteins / genetics*,  metabolism
RNA, Messenger / metabolism*
Time Factors
Ventricular Function, Left
Ventricular Pressure
Reg. No./Substance:
0/Grb14 protein, mouse; 0/MicroRNAs; 0/Proteins; 0/RNA, Messenger; EC 3-Kinase; EC 3-kinase p110 subunit, mouse

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