Influence of heart failure on nucleolar organization and protein expression in human hearts.

Autores de IIS La Fe

• 

  Esther Roselló Lletí

  Autor

• Jose Miguel Rivera Otero

  Autor

• Raquel Cortes Vergaz

  Autor

• Inmaculada Azorín Villena

  Autor

• Rafael Sirera Perez

  Autor

• 

  Luis Vicente Martínez Dolz

  Autor

• José Francisco Dolz Lago

  Autor

• Carlos Gonzalez Juanatey

  Autor

• Antonio Salvador Sanz

  Autor

• Manuel Portoles Sanz

  Autor

Participantes ajenos a IIS La Fe

• Hove L
• Cinca J

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.