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...
Autores principales: | , , , , , , , , , , , |
---|---|
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 |