Please use this identifier to cite or link to this item: http://hdl.handle.net/2067/47021
Title: Proteotoxicity in cardiac amyloidosis: amyloidogenic light chains affect the levels of intracellular proteins in human heart cells
Authors: Imperlini, Esther 
Gnecchi, Massimiliano
Rognoni, Paola
Sabidò, Eduard
Ciuffreda, Maria Chiara
Palladini, Giovanni
Espadas, Guadalupe
Mancuso, Francesco Mattia
Bozzola, Margherita
Malpasso, Giuseppe
Valentini, Veronica
Palladini, Giuseppina
Orrù, Stefania
Ferraro, Giovanni
Milani, Paolo
Perlini, Stefano
Salvatore, Francesco
Merlini, Giampaolo
Lavatelli, Francesca
Journal: SCIENTIFIC REPORTS 
Issue Date: 2017
Abstract: 
AL amyloidosis is characterized by widespread deposition of immunoglobulin light chains (LCs) as amyloid fibrils. Cardiac involvement is frequent and leads to life-threatening cardiomyopathy. Besides the tissue alteration caused by fibrils, clinical and experimental evidence indicates that cardiac damage is also caused by proteotoxicity of prefibrillar amyloidogenic species. As in other amyloidoses, the damage mechanisms at cellular level are complex and largely undefined. We have characterized the molecular changes in primary human cardiac fibroblasts (hCFs) exposed in vitro to soluble amyloidogenic cardiotoxic LCs from AL cardiomyopathy patients. To evaluate proteome alterations caused by a representative cardiotropic LC, we combined gel-based with label-free shotgun analysis and performed bioinformatics and data validation studies. To assess the generalizability of our results we explored the effects of multiple LCs on hCF viability and on levels of a subset of cellular proteins. Our results indicate that exposure of hCFs to cardiotropic LCs translates into proteome remodeling, associated with apoptosis activation and oxidative stress. The proteome alterations affect proteins involved in cytoskeletal organization, protein synthesis and quality control, mitochondrial activity and metabolism, signal transduction and molecular trafficking. These results support and expand the concept that soluble amyloidogenic cardiotropic LCs exert toxic effects on cardiac cells.
URI: http://hdl.handle.net/2067/47021
ISSN: 2045-2322
DOI: 10.1038/s41598-017-15424-3
Rights: Attribution 4.0 International
Appears in Collections:A1. Articolo in rivista

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