Abstract 8413: Differences in Myocyte Enhancer Factor-2 and Nuclear Factor of Activated T Cells Pathways According to Human Heart Failure Aetiology
Introduction: Ca2+ 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 nuclear factor of activated T cells-1 (NFAT1), myocyte enhancer factor-2 (MEF2C) and transcription factor GATA-4 (GATA4); all transcription factors in the same cardiac tissue.
Methods: A total of 80 hearts from ischaemic (ICM, n = 43) and dilated (DCM, n = 31) patients undergoing heart transplantation and controls (n = 6) were analysed by western blotting. Subcellular distribution was analysed by fluorescence and electron microscopy.
Results: We compared Ca+2 handling proteins according to HF aetiology, ICM showed higher levels of calmodulin (27%, p<0.05), calcineurin (22%, p<0.05) and Ca2+/Calmodulin-dependent kinase II (CaMKIIδb nuclear isoform 96%, p<0.01) than control group. However, these proteins in DCM did not significantly increase. Furthermore, ICM showed a significant elevation in MEF2C (23%, p<0.05), and GATA4 (51%, p<0.05); also NFAT1 (53%, p<0.01) was increased, producing the resultant translocation of this transcriptional factor into the nuclei. These results were supported by fluorescence and electron microscopy analysis. In addition, DCM only had a significant increase in GATA4 (52%, p<0.05). Correlations between NFAT1 and MEF2C in both groups (ICM r=0.36 and DCM r=0.51, p<0.05) were found; only ICM showed a correlation between GATA4 and NFAT1 (r=0.42, p<0.05).
Conclusions: This study shows an activation of Ca2+ 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.
- © 2011 by American Heart Association, Inc.