Cyclophilin A/EMMPRIN Axis Is Involved in Pro-Fibrotic Processes Associated with Thoracic Aortic Aneurysm of Marfan Syndrome Patients

Background: Marfan syndrome (MFS) is a genetic disease, characterized by thoracic aortic aneurysm (TAA), which treatment is to date purely surgical. Understanding of novel molecular targets is mandatory to unveil e ective pharmacological approaches. Cyclophilin A (CyPA) and its receptor EMMPRIN are...

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Autores: Perrucci, Gianluca L., Rurali, Erica, Corlianò, Maria, Balzo, Maria, Piccoli, Michela, Moschetta, Donato, Pini, Alessandro, Gaetano, Raffaella, Antona, Carlo, Egea Guri, Gustavo, Fischer, Gunter, Maleševic ́, Miroslav, Alamanni, Francesco, Cogliati, Elisa, Paolin, Adolfo, Pompilio, Giulio, Nigro, Patrizia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/174888
Acceso en línea:https://hdl.handle.net/2445/174888
Access Level:acceso abierto
Palabra clave:Aneurismes aòrtics
Genètica
Aortic aneurysms
Genetics
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spelling Cyclophilin A/EMMPRIN Axis Is Involved in Pro-Fibrotic Processes Associated with Thoracic Aortic Aneurysm of Marfan Syndrome PatientsPerrucci, Gianluca L.Rurali, EricaCorlianò, MariaBalzo, MariaPiccoli, MichelaMoschetta, DonatoPini, AlessandroGaetano, RaffaellaAntona, CarloEgea Guri, GustavoFischer, GunterMaleševic ́, MiroslavAlamanni, FrancescoCogliati, ElisaPaolin, AdolfoPompilio, GiulioNigro, PatriziaAneurismes aòrticsGenèticaAortic aneurysmsGeneticsBackground: Marfan syndrome (MFS) is a genetic disease, characterized by thoracic aortic aneurysm (TAA), which treatment is to date purely surgical. Understanding of novel molecular targets is mandatory to unveil e ective pharmacological approaches. Cyclophilin A (CyPA) and its receptor EMMPRIN are associated with several cardiovascular diseases, including abdominal aortic aneurysm. Here, we envisioned the contribution of CyPA/EMMPRIN axis in MFS-related TAA. Methods: We obtained thoracic aortic samples from healthy controls (HC) and MFS patients' aortas and then isolated vascular smooth muscle cells (VSMC) from the aortic wall. Results: our findings revealed that MFS aortic tissue samples isolated from the dilated zone of aorta showed higher expression levels of EMMPRIN vs. MFS non-dilated aorta and HC. Interestingly, angiotensin II significantly stimulated CyPA secretion in MFS-derived VSMC (MFS-VSMC). CyPA treatment on MFS-VSMC led to increased levels of EMMPRIN and other MFS-associated pro-fibrotic mediators, such as TGF- 1 and collagen I. These molecules were downregulated by in vitro treatment with CyPA inhibitor MM284. Our results suggest that CyPA/EMMPRIN axis is involved in MFS-related TAA development, since EMMPRIN is upregulated in the dilated zone of MFS patients' TAA and the inhibition of its ligand, CyPA, downregulated EMMPRIN and MFS-related markers in MFS-VSMC. Conclusions: these insights suggest both a novel detrimental role for CyPA/EMMPRIN axis and its inhibition as a potential therapeutic strategy for MFS-related TAA treatment.MDPI2021202120202021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion18 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/174888Articles publicats en revistes (Biomedicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3390/cells9010154Cells, 2020, vol. 9, num. 154https://doi.org/10.3390/cells9010154cc-by (c) Perrucci, Gianluca L. et al., 2020http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1748882026-05-29T05:05:01Z
dc.title.none.fl_str_mv Cyclophilin A/EMMPRIN Axis Is Involved in Pro-Fibrotic Processes Associated with Thoracic Aortic Aneurysm of Marfan Syndrome Patients
title Cyclophilin A/EMMPRIN Axis Is Involved in Pro-Fibrotic Processes Associated with Thoracic Aortic Aneurysm of Marfan Syndrome Patients
spellingShingle Cyclophilin A/EMMPRIN Axis Is Involved in Pro-Fibrotic Processes Associated with Thoracic Aortic Aneurysm of Marfan Syndrome Patients
Perrucci, Gianluca L.
Aneurismes aòrtics
Genètica
Aortic aneurysms
Genetics
title_short Cyclophilin A/EMMPRIN Axis Is Involved in Pro-Fibrotic Processes Associated with Thoracic Aortic Aneurysm of Marfan Syndrome Patients
title_full Cyclophilin A/EMMPRIN Axis Is Involved in Pro-Fibrotic Processes Associated with Thoracic Aortic Aneurysm of Marfan Syndrome Patients
title_fullStr Cyclophilin A/EMMPRIN Axis Is Involved in Pro-Fibrotic Processes Associated with Thoracic Aortic Aneurysm of Marfan Syndrome Patients
title_full_unstemmed Cyclophilin A/EMMPRIN Axis Is Involved in Pro-Fibrotic Processes Associated with Thoracic Aortic Aneurysm of Marfan Syndrome Patients
title_sort Cyclophilin A/EMMPRIN Axis Is Involved in Pro-Fibrotic Processes Associated with Thoracic Aortic Aneurysm of Marfan Syndrome Patients
dc.creator.none.fl_str_mv Perrucci, Gianluca L.
Rurali, Erica
Corlianò, Maria
Balzo, Maria
Piccoli, Michela
Moschetta, Donato
Pini, Alessandro
Gaetano, Raffaella
Antona, Carlo
Egea Guri, Gustavo
Fischer, Gunter
Maleševic ́, Miroslav
Alamanni, Francesco
Cogliati, Elisa
Paolin, Adolfo
Pompilio, Giulio
Nigro, Patrizia
author Perrucci, Gianluca L.
author_facet Perrucci, Gianluca L.
Rurali, Erica
Corlianò, Maria
Balzo, Maria
Piccoli, Michela
Moschetta, Donato
Pini, Alessandro
Gaetano, Raffaella
Antona, Carlo
Egea Guri, Gustavo
Fischer, Gunter
Maleševic ́, Miroslav
Alamanni, Francesco
Cogliati, Elisa
Paolin, Adolfo
Pompilio, Giulio
Nigro, Patrizia
author_role author
author2 Rurali, Erica
Corlianò, Maria
Balzo, Maria
Piccoli, Michela
Moschetta, Donato
Pini, Alessandro
Gaetano, Raffaella
Antona, Carlo
Egea Guri, Gustavo
Fischer, Gunter
Maleševic ́, Miroslav
Alamanni, Francesco
Cogliati, Elisa
Paolin, Adolfo
Pompilio, Giulio
Nigro, Patrizia
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Aneurismes aòrtics
Genètica
Aortic aneurysms
Genetics
topic Aneurismes aòrtics
Genètica
Aortic aneurysms
Genetics
description Background: Marfan syndrome (MFS) is a genetic disease, characterized by thoracic aortic aneurysm (TAA), which treatment is to date purely surgical. Understanding of novel molecular targets is mandatory to unveil e ective pharmacological approaches. Cyclophilin A (CyPA) and its receptor EMMPRIN are associated with several cardiovascular diseases, including abdominal aortic aneurysm. Here, we envisioned the contribution of CyPA/EMMPRIN axis in MFS-related TAA. Methods: We obtained thoracic aortic samples from healthy controls (HC) and MFS patients' aortas and then isolated vascular smooth muscle cells (VSMC) from the aortic wall. Results: our findings revealed that MFS aortic tissue samples isolated from the dilated zone of aorta showed higher expression levels of EMMPRIN vs. MFS non-dilated aorta and HC. Interestingly, angiotensin II significantly stimulated CyPA secretion in MFS-derived VSMC (MFS-VSMC). CyPA treatment on MFS-VSMC led to increased levels of EMMPRIN and other MFS-associated pro-fibrotic mediators, such as TGF- 1 and collagen I. These molecules were downregulated by in vitro treatment with CyPA inhibitor MM284. Our results suggest that CyPA/EMMPRIN axis is involved in MFS-related TAA development, since EMMPRIN is upregulated in the dilated zone of MFS patients' TAA and the inhibition of its ligand, CyPA, downregulated EMMPRIN and MFS-related markers in MFS-VSMC. Conclusions: these insights suggest both a novel detrimental role for CyPA/EMMPRIN axis and its inhibition as a potential therapeutic strategy for MFS-related TAA treatment.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/174888
url https://hdl.handle.net/2445/174888
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/cells9010154
Cells, 2020, vol. 9, num. 154
https://doi.org/10.3390/cells9010154
dc.rights.none.fl_str_mv cc-by (c) Perrucci, Gianluca L. et al., 2020
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Perrucci, Gianluca L. et al., 2020
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 18 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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