Heart failure entails significant changes in human nucleocytoplasmic transport gene expression

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• 作者：Maria Micaela Molina-Navarro ; Esther Rosell¨®-Llet¨ª ; Estefan¨ªa Taraz¨®n ; Ana Ortega ; Dolors S¨¢nchez-Izquierdo ; Francisca Lago ; Jos¨¦ Ram¨®n Gonz¨¢lez-Juanatey ; Pablo Garc¨ªa-Pav¨ªa ; Antonio Salvador ; Jos¨¦ Anastasio Montero ; Manuel Portol¨¦s ; Miguel Rivera
• 关键词：Heart failure ; Dilated cardiomyopathy ; Ischemic cardiomyopathy ; Microarray ; Nucleocytoplasmic transport ; XPO1
• 刊名：International Journal of Cardiology
• 出版年：2013
• 出版时间：3 October, 2013
• 年：2013
• 卷：168
• 期：3
• 页码：2837-2843
• 全文大小：935 K

文摘

Background

Heart failure (HF) induces alterations in nucleocytoplasmic transport, which is essential to the cardiomyocyte biology. The objective of this study was to analyze the changes in gene expression in human HF, particularly focusing on nucleocytoplasmic transport-related genes.

Methods and results

29 RNA heart samples from dilated cardiomyopathy (DCM, n = 12) and ischemic cardiomyopathy (ICM, n = 12) patients undergoing heart transplantation and control donors (CNT, n = 5) were extracted to perform a microarray profiling using Affymetrix Human Gene? 1.0 ST arrays. We focused on the study of 5 nucleocytoplasmic transport-related genes, since this functional category has not previously been studied in HF. XPO1, GABPB2, and RANBP17 were upregulated, while KALRN was downregulated in both DCM and ICM, and XPO5 only in DCM. Validation of the results by RT-qPCR increasing the total heart samples up to 41 showed a high degree of consistency with microarray results. Moreover, we observed a strong relationship between the XPO1 mRNA and robust left ventricular function parameters in ICM: left ventricular end-systolic (r = 0.81, p < 0.0001) and end-diastolic diameters (r = 0.80, p < 0.0001), and ejection fraction (r = ? 0.57, p < 0.05).

Conclusions

We show that the expression of nucleocytoplasmic transport-related genes is altered in HF. Furthermore, XPO1 mRNA level is closely related with robust left ventricular function parameters in ICM patients. These changes may help to distinguish DCM and ICM in HF at the level of the transcriptome and provide a base for novel therapeutic approaches.