title: Heart failure induces significant changes in nuclear pore complex of human cardiomyocytes.
abstract: OBJECTIVE
  The objectives of this study were to analyse the effect of heart failure (HF) on several proteins of nuclear pore complex (NPC) and their relationship with the human ventricular function.
  
  
  RESULTS
  A total of 88 human heart samples from ischemic (ICM, n = 52) and dilated (DCM, n = 36) patients undergoing heart transplant and control donors (CNT, n = 9) were analyzed by Western blot. Subcellular distribution of nucleoporins was analysed by fluorescence and immunocytochemistry. When we compared protein levels according to etiology, ICM showed significant higher levels of NDC1 (65%, p<0.0001), Nup160 (88%, p<0.0001) and Nup153 (137%, p = 0.004) than those of the CNT levels. Furthermore, DCM group showed significant differences for NDC1 (41%, p<0.0001), Nup160 (65%, p<0.0001), Nup153 (155%, p = 0.006) and Nup93 (88%, p<0.0001) compared with CNT. However, Nup155 and translocated promoter region (TPR) did not show significant differences in their levels in any etiology. Regarding the distribution of these proteins in cell nucleus, only NDC1 showed differences in HF. In addition, in the pathological group we obtained good relationship between the ventricular function parameters (LVEDD and LVESD) and Nup160 (r = -0382, p = 0.004; r = -0.290, p = 0.033; respectively).
  
  
  CONCLUSIONS
  This study shows alterations in specific proteins (NDC1, Nup160, Nup153 and Nup93) that compose NPC in ischaemic and dilated human heart. These changes, related to ventricular function, could be accompanied by alterations in the nucleocytoplasmic transport. Therefore, our findings may be the basis for a new approach to HF management.
authors.affiliation: Cardiocirculatory Unit, Research Center, Hospital Universitario La Fe, Valencia, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Tarazón
authors.forename: Miguel
authors.initials: M
authors.lastname: Rivera
authors.forename: Esther
authors.initials: E
authors.lastname: Roselló-Lletí
authors.forename: Maria Micaela
authors.initials: MM
authors.lastname: Molina-Navarro
authors.forename: Ignacio José
authors.initials: IJ
authors.lastname: Sánchez-Lázaro
authors.forename: Francisco
authors.initials: F
authors.lastname: España
authors.forename: José Anastasio
authors.initials: JA
authors.lastname: Montero
authors.forename: Francisca
authors.initials: F
authors.lastname: Lago
authors.forename: José Ramón
authors.initials: JR
authors.lastname: González-Juanatey
authors.forename: Manuel
authors.initials: M
authors.lastname: Portolés
mesh_terms: D000328:Adult; D005260:Female; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D021381:Protein Transport
chemical_list: C510249:NDC1 protein, human; C440251:NUP160 protein, human; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins