Abstract 11011: Heart Failure Influences Nucleolar Organization and Protein Expression in Human Hearts
Introduction: The nucleolus represents a dynamic structure involved in important cellular processes, but its role in development of heart failure (HF) has not been studied.
Methods: We investigate for the first time the influence of HF on nucleolar organization and proteins in patients with ischemic (ICM) or dilated cardiomyopathy (DCM). A total of 75 human hearts from ICM (n=38) and DCM (n=31) patients, undergoing heart transplantation and control donors (n=6), were analysed by western-blotting and gene expression methods.
Results: 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). Fibrillarin, B23 and MDM2 were not different when compared with control donors. 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). Finally, 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).
Conclusions: 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. This work established a new way for further studies that analyze other factors involved in the nucleolus activity that could alter several nuclear functions and that could be potential drug targets in human HF.
- © 2012 by American Heart Association, Inc.