Document Detail

Differences in MEF2 and NFAT transcriptional pathways according to human heart failure aetiology.
MedLine Citation:
PMID:  22363514     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Ca(2+) handling machinery modulates the activation of cardiac transcription pathways involved in heart failure (HF). The present study investigated the effect of HF aetiology on Ca(+2) handling proteins and NFAT1, MEF2C and GATA4 (transcription factors) in the same cardiac tissue.
METHODOLOGY AND PRINCIPAL FINDINGS: A total of 83 hearts from ischemic (ICM, n = 43) and dilated (DCM, n = 31) patients undergoing heart transplantation and controls (CNT, n = 9) were analyzed by western blotting. Subcellular distribution was analyzed by fluorescence and electron microscopy. When we compared Ca(+2) handling proteins according to HF aetiology, ICM showed higher levels of calmodulin (24%, p<0.01), calcineurin (26%, p<0.01) and Ca(2+)/Calmodulin-dependent kinase II (CaMKIIδ(b) nuclear isoform 62%, p<0.001) than the CNT group. However, these proteins in DCM did not significantly increase. Furthermore, ICM showed a significant elevation in MEF2C (33%, p<0.01), and GATA4 (49%, p<0.05); also NFAT1 (66%, p<0.001) was increased, producing the resultant translocation of this transcriptional factor into the nuclei. These results were supported by fluorescence and electron microscopy analysis. Whereas, DCM only had a significant increase in GATA4 (52%, p<0.05). Correlations between NFAT1 and MEF2C in both groups (ICM r = 0.38 and DCM r = 0.59, p<0.05 and p<0.01, respectively) were found; only ICM showed a correlation between GATA4 and NFAT1 (r = 0.37, p<0.05).
CONCLUSIONS/SIGNIFICANCE: This study shows an increase of Ca(2+) handling machinery synthesis and their cardiac transcription pathways in HF, being more markedly increased in ICM. Furthermore, there is a significant association between MEF2, NFAT1 and GATA4. These proteins could be therapeutic targets to improve myocardial function.
Raquel Cortés; Miguel Rivera; Esther Roselló-Lletí; Luis Martínez-Dolz; Luis Almenar; Inmaculada Azorín; Francisca Lago; José Ramón González-Juanatey; Manuel Portolés
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-02-17
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-02-24     Completed Date:  2012-06-29     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e30915     Citation Subset:  IM    
Cardiocirculatory Unit, Research Center, Hospital Universitario La Fe, Valencia, Spain.
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MeSH Terms
Blotting, Western
Calcineurin / metabolism
Calcium / metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
Calmodulin / metabolism
GATA4 Transcription Factor / metabolism
Heart Failure / enzymology,  etiology*,  genetics*,  ultrasonography
Heterochromatin / metabolism,  ultrastructure
MADS Domain Proteins / genetics*,  metabolism
Middle Aged
Myocardium / metabolism,  pathology
Myocytes, Cardiac / metabolism,  pathology,  ultrastructure
Myogenic Regulatory Factors / genetics*,  metabolism
NFATC Transcription Factors / genetics*,  metabolism
Protein Transport
Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism
Signal Transduction / genetics*
Sodium-Calcium Exchanger / metabolism
Subcellular Fractions / enzymology
Transcription, Genetic*
Reg. No./Substance:
0/Calmodulin; 0/GATA4 Transcription Factor; 0/GATA4 protein, human; 0/Heterochromatin; 0/MADS Domain Proteins; 0/MEF2C protein, human; 0/Myogenic Regulatory Factors; 0/NFATC Transcription Factors; 0/NFATC2 protein, human; 0/Sodium-Calcium Exchanger; 0/sodium-calcium exchanger 1; 7440-70-2/Calcium; EC Protein Kinase Type 2; EC; EC protein, human; EC Reticulum Calcium-Transporting ATPases

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