title: Influence of heart failure on nucleolar organization and protein expression in human hearts.
abstract: We investigate for the first time the influence of heart failure (HF) on nucleolar organization and proteins in patients with ischemic (ICM) or dilated cardiomyopathy (DCM). A total of 71 human hearts from ICM (n=38) and DCM (n=27) patients, undergoing heart transplantation and control donors (n=6), were analysed by western-blotting, RT-PCR and cell biology methods. When we compared protein levels according to HF etiology, nucleolin was increased in both ICM (117%, p<0.05) and DCM (141%, p<0.01). Moreover, mRNA expression were also upregulated in ICM (1.46-fold, p<0.05) and DCM (1.70-fold, p<0.05. Immunofluorescence studies showed that the highest intensity of nucleolin was into nucleolus (p<0.0001), and it was increased in pathological hearts (p<0.0001). Ultrastructure analysis by electron microscopy showed an increase in the nucleus and nucleolus size in ICM (17%, p<0.05 and 131%, p<0.001) and DCM (56%, p<0.01 and 69%, p<0.01). Nucleolar organization was influenced by HF irrespective of etiology, increasing fibrillar centers (p<0.001), perinucleolar chromatin (p<0.01) and dense fibrillar components (p<0.01). Finally, left ventricular function parameters were related with nucleolin levels in ischemic hearts (p<0.0001). The present study demonstrates that HF influences on morphology and organization of nucleolar components, revealing changes in the expression and in the levels of nucleolin protein.
authors.affiliation: Cardiocirculatory Unit, Research Center, Hospital Universitario La Fe, Valencia, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Roselló-Lletí
authors.forename: Miguel
authors.initials: M
authors.lastname: Rivera
authors.forename: Raquel
authors.initials: R
authors.lastname: Cortés
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Azorín
authors.forename: Rafael
authors.initials: R
authors.lastname: Sirera
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Dolz
authors.forename: Leif
authors.initials: L
authors.lastname: Hove
authors.forename: Juan
authors.initials: J
authors.lastname: Cinca
authors.forename: Francisca
authors.initials: F
authors.lastname: Lago
authors.forename: José R
authors.initials: JR
authors.lastname: González-Juanatey
authors.forename: Antonio
authors.initials: A
authors.lastname: Salvador
authors.forename: Manuel
authors.initials: M
authors.lastname: Portolés
mesh_terms: D002311:Cardiomyopathy, Dilated / Q000150:complications; D002466:Cell Nucleolus / Q000648:ultrastructure*; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis; D005260:Female; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D009687:Nuclear Proteins / Q000096:biosynthesis*; D000090243:Nucleophosmin; D010750:Phosphoproteins / Q000096:biosynthesis; D014176:Protein Biosynthesis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000096:biosynthesis; D016601:RNA-Binding Proteins / Q000096:biosynthesis; D000097796:Nucleolin
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D010750:Phosphoproteins; D051736:Proto-Oncogene Proteins c-mdm2; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C047458:fibrillarin; C497206:MDM2 protein, human