Document Detail


Myocardial expression of FOXO3a-Atrogin-1 pathway in human heart failure.
MedLine Citation:
PMID:  21098579     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Gennaro Galasso; Roberta De Rosa; Federico Piscione; Guido Iaccarino; Carlo Vosa; Daniela Sorriento; Raffaele Piccolo; Antonio Rapacciuolo; Kenneth Walsh; Massimo Chiariello
Related Documents :
20625799 - Altered expression of pro- and anti-inflammatory cytokines is associated with reduced c...
19043979 - Changes in ecg and enzyme activity in rat heart after myocardial infarction: effect of ...
20579749 - Oestradiol supplement minimises coronary occlusion-induced myocardial infarction and ve...
15364619 - Reciprocal regulation of angiopoietin-1 and angiopoietin-2 following myocardial infarct...
23594699 - Left ventricular assist devices: from the bench to the clinic.
8934519 - Inhibition of myocardial endothelin pathway improves long-term survival in heart failure.
14740239 - Prognostic significance of the signal averaged electrocardiogram in patients with chron...
18852589 - Percutaneous transluminal coronary angioplasty hardware entrapment: guidewire entrapment.
23067909 - A 2-hour thrombolysis in myocardial infarction score outperforms other risk stratificat...
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    
Affiliation:
Department of Clinical Medicine, Cardiovascular and Immunology Sciences, Federico II University School of Medicine, Via S. Pansini, 5, 80131 Naples, Italy.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
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:
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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Improved diabetic control in advanced heart failure patients treated with left ventricular assist de...
Next Document:  Telemedical Interventional Monitoring in Heart Failure (TIM-HF), a randomized, controlled interventi...