| Myocardial expression of FOXO3a-Atrogin-1 pathway in human heart failure. | |
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MedLine Citation:
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PMID: 21098579 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS: Several studies have shown that muscle mass loss is an important pathogenic issue in heart failure (HF). Atrogin-1 is a F-box protein selectively expressed in cardiac and skeletal muscle tissue, which plays a pivotal role in muscle wasting regulation. The aim of this study was to investigate the expression of Atrogin-1 and the molecular pathway involved in Atrogin-1 regulation in human HF. METHODS AND RESULTS: Cardiac tissue from patients with HF (HF group: n=10) or with normal left ventricular function (control group: n=9) was studied by western blot and real time-PCR analysis. Linear regression analysis between patients left ventricular ejection fraction (LVEF) and Atrogin1 or its regulator Forkhead box O 3a (Foxo3a) myocardial expression was performed to test correlations between protein expression and LVEF. Western blot analysis revealed that the myocardial expression of Atrogin-1 in the HF group was 2.5-fold increased compared with controls (P=0.007). Accordingly, Atrogin-1 mRNA was 1.5 higher than in controls (P=0.003). The expression of Foxo3a and its up-stream regulator AKT were also measured. Western blot analysis demonstrated in the HF group a 2.56-fold reduction of AKT phosphorylation and a 3.32-fold increase of Foxo3a as compared with controls (P=0.002 and P=0.001, respectively). Finally, linear regression showed a significant relationship between Foxo3a or Atrogin-1 expression and LVEF (R=0.976, P<0.0001 and R=0.895, P=0.003, respectively). CONCLUSION: Our results suggest that in human HF, the activity of AKT decreases, with activation of Foxo3a and induction of Atrogin-1, thereby leading to a molecular state that favours heart muscle loss and left ventricular dysfunction. |
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Authors:
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Gennaro Galasso; Roberta De Rosa; Federico Piscione; Guido Iaccarino; Carlo Vosa; Daniela Sorriento; Raffaele Piccolo; Antonio Rapacciuolo; Kenneth Walsh; Massimo Chiariello |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: European journal of heart failure Volume: 12 ISSN: 1879-0844 ISO Abbreviation: Eur. J. Heart Fail. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-24 Completed Date: 2011-06-02 Revised Date: 2011-06-08 |
Medline Journal Info:
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Nlm Unique ID: 100887595 Medline TA: Eur J Heart Fail Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1290-6 Citation Subset: IM |
Affiliation:
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Department of Clinical Medicine, Cardiovascular and Immunology Sciences, Federico II University School of Medicine, Via S. Pansini, 5, 80131 Naples, Italy. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Blotting, Western Case-Control Studies Confidence Intervals Female Forkhead Transcription Factors / metabolism* Heart Failure / drug therapy, enzymology, pathology* Humans Linear Models Male Middle Aged Muscle Proteins / metabolism* Myocardium / enzymology*, pathology Phosphorylation SKP Cullin F-Box Protein Ligases / metabolism* Statistics as Topic Ventricular Function, Left |
| Chemical | |
Reg. No./Substance:
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0/FOXO3 protein, human; 0/Forkhead Transcription Factors; 0/Muscle Proteins; EC 6.3.2.19/FBXO32 protein, human; EC 6.3.2.19/SKP Cullin F-Box Protein Ligases |
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