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

Esther Roselló-Lletí1, Miguel Rivera, Raquel Cortés

  • 1Cardiocirculatory Unit, Research Center, Hospital Universitario La Fe, Valencia, Spain.

Insights

Heart failure (HF) alters nucleolar organization and increases nucleolin protein levels in patients with ischemic (ICM) and dilated cardiomyopathy (DCM). These findings reveal significant changes in cellular structures due to heart disease.

Area of Science:

  • Cardiovascular Biology
  • Cellular Biology
  • Molecular Cardiology

Background:

  • Heart failure (HF) is a complex syndrome impacting cardiac function.
  • The role of nucleolar organization and proteins in HF pathogenesis remains largely unexplored.
  • Understanding these cellular changes may offer new insights into HF mechanisms.

Purpose of the Study:

  • To investigate the influence of heart failure (HF) on nucleolar organization and protein levels.
  • To compare these effects in patients with ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM).

Main Methods:

  • Analysis of 71 human heart samples (ICM, DCM, and controls) using Western blotting, RT-PCR, immunofluorescence, and electron microscopy.
  • Quantification of nucleolin protein and mRNA expression.
  • Assessment of nucleolar morphology and ultrastructure.

Main Results:

  • Nucleolin protein and mRNA levels were significantly upregulated in both ICM and DCM hearts compared to controls.
  • Immunofluorescence confirmed increased nucleolin intensity within the nucleolus in pathological hearts.
  • Ultrastructural analysis revealed enlarged nucleus and nucleolus size, with altered nucleolar organization (increased fibrillar centers, perinucleolar chromatin, and dense fibrillar components) in HF.
  • Left ventricular function correlated with nucleolin levels in ICM.

Conclusions:

  • Heart failure, irrespective of etiology, significantly influences nucleolar morphology and organization.
  • Expression and levels of nucleolin protein are altered in the failing heart.
  • These findings highlight a novel link between cardiac dysfunction and nucleolar alterations.

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