Document Detail

Myocardial expression of FOXO3a-Atrogin-1 pathway in human heart failure.
MedLine Citation:
PMID:  21098579     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article    
Journal Detail:
Title:  European journal of heart failure     Volume:  12     ISSN:  1879-0844     ISO Abbreviation:  Eur. J. Heart Fail.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2011-06-02     Revised Date:  2011-06-08    
Medline Journal Info:
Nlm Unique ID:  100887595     Medline TA:  Eur J Heart Fail     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1290-6     Citation Subset:  IM    
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
Blotting, Western
Case-Control Studies
Confidence Intervals
Forkhead Transcription Factors / metabolism*
Heart Failure / drug therapy,  enzymology,  pathology*
Linear Models
Middle Aged
Muscle Proteins / metabolism*
Myocardium / enzymology*,  pathology
SKP Cullin F-Box Protein Ligases / metabolism*
Statistics as Topic
Ventricular Function, Left
Reg. No./Substance:
0/FOXO3 protein, human; 0/Forkhead Transcription Factors; 0/Muscle Proteins; EC protein, human; EC Cullin F-Box Protein Ligases

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