Differences in MEF2 and NFAT transcriptional pathways according to human heart failure aetiology.
Differences in MEF2 and NFAT transcriptional pathways according to human heart failure aetiology.
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DOI：
10.1371/journal.pone.0030915
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Portolés M
中科院分区：
文献类型：
--
作者：
Cortés R;Rivera M;Roselló-Lletí E;Martínez-Dolz L;Almenar L;Azorín I;Lago F;González-Juanatey JR;Portolés M
Ca 2+处理机制调节心力衰竭（HF）中涉及的心脏转录途径的激活。本研究探讨了HF病因学对同一心脏组织中Ca+2处理蛋白和NFAT 1、MEF 2C和GATA 4（转录因子）的影响。共83个心脏缺血（ICM，n = 43）和扩张（DCM，n = 31）患者接受心脏移植和对照组（CNT，n = 9）进行了分析。 通过荧光显微镜和电子显微镜分析亚细胞分布。当我们根据HF病因学比较Ca+2处理蛋白时，ICM显示出比CNT组更高水平的钙调蛋白（24%，p<0.01）、钙调神经磷酸酶（26%，p<0.01）和Ca 2 +/钙调蛋白依赖性激酶II（CaMK II δB核同种型62%，p<0.001）。然而，这些蛋白质在DCM中没有显著增加。此外，ICM显示MEF 2C（33%，p<0.01）和GATA 4（49%，p<0.05）显著升高; NFAT 1（66%，p<0.001）也增加，导致该转录因子易位到细胞核中。这些结果得到了荧光和电子显微镜分析的支持。而DCM组仅GATA 4显著升高（52%，p<0.05）。在两组中发现NFAT 1和MEF 2C之间的相关性（ICM r = 0.38和DCM r = 0.59，分别为p<0.05和p<0.01）;仅ICM显示GATA 4和NFAT 1之间的相关性（r = 0.37，p<0.05）。 这项研究表明，在HF中，Ca 2+处理机制的合成及其心脏转录途径增加，在ICM中更显着增加。此外，MEF 2、NFAT 1和GATA 4之间存在显著关联。这些蛋白可能是改善心肌功能的治疗靶点。
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 NFAT1, MEF2C and GATA4 (transcription factors) in the same cardiac tissue. 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 Ca2+/Calmodulin-dependent kinase II (CaMKIIδb 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). This study shows an increase 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.
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影响因子：
10.8
作者：
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发表时间：
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影响因子：
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