Cargando…

Excess TGF-β1 Drives Cardiac Mesenchymal Stromal Cells to a Pro-Fibrotic Commitment in Arrhythmogenic Cardiomyopathy

Arrhythmogenic Cardiomyopathy (ACM) is characterized by the replacement of the myocardium with fibrotic or fibro-fatty tissue and inflammatory infiltrates in the heart. To date, while ACM adipogenesis is a well-investigated differentiation program, ACM-related fibrosis remains a scientific gap of kn...

Descripción completa

Detalles Bibliográficos
Autores principales: Maione, Angela Serena, Stadiotti, Ilaria, Pilato, Chiara Assunta, Perrucci, Gianluca Lorenzo, Saverio, Valentina, Catto, Valentina, Vettor, Giulia, Casella, Michela, Guarino, Anna, Polvani, Gianluca, Pompilio, Giulio, Sommariva, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961797/
https://www.ncbi.nlm.nih.gov/pubmed/33800912
http://dx.doi.org/10.3390/ijms22052673
_version_ 1783665340230664192
author Maione, Angela Serena
Stadiotti, Ilaria
Pilato, Chiara Assunta
Perrucci, Gianluca Lorenzo
Saverio, Valentina
Catto, Valentina
Vettor, Giulia
Casella, Michela
Guarino, Anna
Polvani, Gianluca
Pompilio, Giulio
Sommariva, Elena
author_facet Maione, Angela Serena
Stadiotti, Ilaria
Pilato, Chiara Assunta
Perrucci, Gianluca Lorenzo
Saverio, Valentina
Catto, Valentina
Vettor, Giulia
Casella, Michela
Guarino, Anna
Polvani, Gianluca
Pompilio, Giulio
Sommariva, Elena
author_sort Maione, Angela Serena
collection PubMed
description Arrhythmogenic Cardiomyopathy (ACM) is characterized by the replacement of the myocardium with fibrotic or fibro-fatty tissue and inflammatory infiltrates in the heart. To date, while ACM adipogenesis is a well-investigated differentiation program, ACM-related fibrosis remains a scientific gap of knowledge. In this study, we analyze the fibrotic process occurring during ACM pathogenesis focusing on the role of cardiac mesenchymal stromal cells (C-MSC) as a source of myofibroblasts. We performed the ex vivo studies on plasma and right ventricular endomyocardial bioptic samples collected from ACM patients and healthy control donors (HC). In vitro studies were performed on C-MSC isolated from endomyocardial biopsies of both groups. Our results revealed that circulating TGF-β1 levels are significantly higher in the ACM cohort than in HC. Accordingly, fibrotic markers are increased in ACM patient-derived cardiac biopsies compared to HC ones. This difference is not evident in isolated C-MSC. Nevertheless, ACM C-MSC are more responsive than HC ones to TGF-β1 treatment, in terms of pro-fibrotic differentiation and higher activation of the SMAD2/3 signaling pathway. These results provide the novel evidence that C-MSC are a source of myofibroblasts and participate in ACM fibrotic remodeling, being highly responsive to ACM-characteristic excess TGF-β1.
format Online
Article
Text
id pubmed-7961797
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-79617972021-03-17 Excess TGF-β1 Drives Cardiac Mesenchymal Stromal Cells to a Pro-Fibrotic Commitment in Arrhythmogenic Cardiomyopathy Maione, Angela Serena Stadiotti, Ilaria Pilato, Chiara Assunta Perrucci, Gianluca Lorenzo Saverio, Valentina Catto, Valentina Vettor, Giulia Casella, Michela Guarino, Anna Polvani, Gianluca Pompilio, Giulio Sommariva, Elena Int J Mol Sci Article Arrhythmogenic Cardiomyopathy (ACM) is characterized by the replacement of the myocardium with fibrotic or fibro-fatty tissue and inflammatory infiltrates in the heart. To date, while ACM adipogenesis is a well-investigated differentiation program, ACM-related fibrosis remains a scientific gap of knowledge. In this study, we analyze the fibrotic process occurring during ACM pathogenesis focusing on the role of cardiac mesenchymal stromal cells (C-MSC) as a source of myofibroblasts. We performed the ex vivo studies on plasma and right ventricular endomyocardial bioptic samples collected from ACM patients and healthy control donors (HC). In vitro studies were performed on C-MSC isolated from endomyocardial biopsies of both groups. Our results revealed that circulating TGF-β1 levels are significantly higher in the ACM cohort than in HC. Accordingly, fibrotic markers are increased in ACM patient-derived cardiac biopsies compared to HC ones. This difference is not evident in isolated C-MSC. Nevertheless, ACM C-MSC are more responsive than HC ones to TGF-β1 treatment, in terms of pro-fibrotic differentiation and higher activation of the SMAD2/3 signaling pathway. These results provide the novel evidence that C-MSC are a source of myofibroblasts and participate in ACM fibrotic remodeling, being highly responsive to ACM-characteristic excess TGF-β1. MDPI 2021-03-06 /pmc/articles/PMC7961797/ /pubmed/33800912 http://dx.doi.org/10.3390/ijms22052673 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Maione, Angela Serena
Stadiotti, Ilaria
Pilato, Chiara Assunta
Perrucci, Gianluca Lorenzo
Saverio, Valentina
Catto, Valentina
Vettor, Giulia
Casella, Michela
Guarino, Anna
Polvani, Gianluca
Pompilio, Giulio
Sommariva, Elena
Excess TGF-β1 Drives Cardiac Mesenchymal Stromal Cells to a Pro-Fibrotic Commitment in Arrhythmogenic Cardiomyopathy
title Excess TGF-β1 Drives Cardiac Mesenchymal Stromal Cells to a Pro-Fibrotic Commitment in Arrhythmogenic Cardiomyopathy
title_full Excess TGF-β1 Drives Cardiac Mesenchymal Stromal Cells to a Pro-Fibrotic Commitment in Arrhythmogenic Cardiomyopathy
title_fullStr Excess TGF-β1 Drives Cardiac Mesenchymal Stromal Cells to a Pro-Fibrotic Commitment in Arrhythmogenic Cardiomyopathy
title_full_unstemmed Excess TGF-β1 Drives Cardiac Mesenchymal Stromal Cells to a Pro-Fibrotic Commitment in Arrhythmogenic Cardiomyopathy
title_short Excess TGF-β1 Drives Cardiac Mesenchymal Stromal Cells to a Pro-Fibrotic Commitment in Arrhythmogenic Cardiomyopathy
title_sort excess tgf-β1 drives cardiac mesenchymal stromal cells to a pro-fibrotic commitment in arrhythmogenic cardiomyopathy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961797/
https://www.ncbi.nlm.nih.gov/pubmed/33800912
http://dx.doi.org/10.3390/ijms22052673
work_keys_str_mv AT maioneangelaserena excesstgfb1drivescardiacmesenchymalstromalcellstoaprofibroticcommitmentinarrhythmogeniccardiomyopathy
AT stadiottiilaria excesstgfb1drivescardiacmesenchymalstromalcellstoaprofibroticcommitmentinarrhythmogeniccardiomyopathy
AT pilatochiaraassunta excesstgfb1drivescardiacmesenchymalstromalcellstoaprofibroticcommitmentinarrhythmogeniccardiomyopathy
AT perruccigianlucalorenzo excesstgfb1drivescardiacmesenchymalstromalcellstoaprofibroticcommitmentinarrhythmogeniccardiomyopathy
AT saveriovalentina excesstgfb1drivescardiacmesenchymalstromalcellstoaprofibroticcommitmentinarrhythmogeniccardiomyopathy
AT cattovalentina excesstgfb1drivescardiacmesenchymalstromalcellstoaprofibroticcommitmentinarrhythmogeniccardiomyopathy
AT vettorgiulia excesstgfb1drivescardiacmesenchymalstromalcellstoaprofibroticcommitmentinarrhythmogeniccardiomyopathy
AT casellamichela excesstgfb1drivescardiacmesenchymalstromalcellstoaprofibroticcommitmentinarrhythmogeniccardiomyopathy
AT guarinoanna excesstgfb1drivescardiacmesenchymalstromalcellstoaprofibroticcommitmentinarrhythmogeniccardiomyopathy
AT polvanigianluca excesstgfb1drivescardiacmesenchymalstromalcellstoaprofibroticcommitmentinarrhythmogeniccardiomyopathy
AT pompiliogiulio excesstgfb1drivescardiacmesenchymalstromalcellstoaprofibroticcommitmentinarrhythmogeniccardiomyopathy
AT sommarivaelena excesstgfb1drivescardiacmesenchymalstromalcellstoaprofibroticcommitmentinarrhythmogeniccardiomyopathy