Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder characterized by the progressive substitution of functional myocardium with noncontractile fibro-fatty tissue contributing to ventricular arrhythmias and sudden cardiac death. Cyclophilin A (CyPA) is a ubiquitous protein involved in several pathological mechanisms, which also characterize ACM (i.e., fibrosis, inflammation, and adipogenesis). Nevertheless, the involvement of CyPA in ACM cardiac remodeling has not been investigated yet. Thus, we first evaluated CyPA expression levels in the right ventricle (RV) tissue specimens obtained from ACM patients and healthy controls (HC) by immunohistochemistry. Then, we took advantage of ACM-and HC-derived cardiac mesenchymal stromal cells (C-MSC) to assess CyPA modulation during adipogenic differentiation. Interestingly, CyPA was more expressed in the RV sections obtained from ACM vs. HC subjects and positively correlated with the adipose replacement extent. Moreover, CyPA was upregulated at early stages of C-MSC adipogenic differentiation and was secreted at higher level over time in ACM-derived C-MSC. Our study provides novel ex vivo and in vitro information on CyPA expression in ACM remodeling paving the way for future C-MSC-based mechanistic and therapeutic investigations.
Cyclophilin a in arrhythmogenic cardiomyopathy cardiac remodeling / E. Rurali, C.A. Pilato, G.L. Perrucci, A. Scopece, I. Stadiotti, D. Moschetta, M. Casella, E. Cogliati, E. Sommariva, G. Pompilio, P. Nigro. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 20:10(2019 May 15), pp. 2403.1-2403.10.
|Titolo:||Cyclophilin a in arrhythmogenic cardiomyopathy cardiac remodeling|
|Parole Chiave:||Adipogenesis; Arrhythmogenic cardiomyopathy; Cardiac mesenchymal stromal cells; Cyclophilin A; Fibrosis; Adipogenesis; Adipose Tissue; Arrhythmias, Cardiac; Cardiomyopathies; Cell Differentiation; Cyclophilin A; Death, Sudden, Cardiac; Fibrosis; Gene Expression; Heart Ventricles; Humans; Inflammation; Mesenchymal Stem Cells; Myocardium; Ventricular Remodeling|
|Settore Scientifico Disciplinare:||Settore MED/11 - Malattie dell'Apparato Cardiovascolare|
Settore BIO/14 - Farmacologia
Settore MED/23 - Chirurgia Cardiaca
|Data di pubblicazione:||15-mag-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3390/ijms20102403|
|Appare nelle tipologie:||01 - Articolo su periodico|