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

Abstract

[EN] 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. © 2012 Elsevier Inc.