title: Heart failure entails significant changes in human nucleocytoplasmic transport gene expression.
abstract: 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.
  
  
  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.
authors: Cardiocirculatory Unit, Health Research Institute Hospital La Fe, Valencia, Spain.
authors: Maria Micaela
authors: MM
authors: Molina-Navarro
authors: Esther
authors: E
authors: Roselló-Lletí
authors: Estefanía
authors: E
authors: Tarazón
authors: Ana
authors: A
authors: Ortega
authors: Dolors
authors: D
authors: Sánchez-Izquierdo
authors: Francisca
authors: F
authors: Lago
authors: José Ramón
authors: JR
authors: González-Juanatey
authors: Pablo
authors: P
authors: García-Pavía
authors: Antonio
authors: A
authors: Salvador
authors: José Anastasio
authors: JA
authors: Montero
authors: Manuel
authors: M
authors: Portolés
authors: Miguel
authors: M
authors: Rivera
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged
keywords: Dilated cardiomyopathy; Heart failure; Ischemic cardiomyopathy; Microarray; Nucleocytoplasmic transport; XPO1