NADPH oxidase 4 attenuates cerebral artery changes during the progression of Marfan syndrome

Marfan syndrome (MFS) is a connective tissue disorder that is often associated with the fibrillin-1 (Fbn1) gene mutation and characterized by cardiovascular alterations, predominantly ascending aortic aneurysms. Although neurovascular complications are uncommon in MFS, the improvement in Marfan pati...

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Detalhes bibliográficos
Autores: Onetti, Yara, Meirelles, Thayna, Dantas, Ana Paula, Schröder, Katrin, Vila, Elisabet, Egea Guri, Gustavo, Jiménez Altayó, Francesc
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2016
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/102549
Acesso em linha:https://hdl.handle.net/2445/102549
Access Level:acceso abierto
Palavra-chave:Teixit connectiu
Malalties hereditàries
Aneurismes aòrtics
Factors de creixement
Connective tissue
Genetic diseases
Aortic aneurysms
Growth factors
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spelling NADPH oxidase 4 attenuates cerebral artery changes during the progression of Marfan syndromeOnetti, YaraMeirelles, ThaynaDantas, Ana PaulaSchröder, KatrinVila, ElisabetEgea Guri, GustavoJiménez Altayó, FrancescTeixit connectiuMalalties hereditàriesAneurismes aòrticsFactors de creixementConnective tissueGenetic diseasesAortic aneurysmsGrowth factorsMarfan syndrome (MFS) is a connective tissue disorder that is often associated with the fibrillin-1 (Fbn1) gene mutation and characterized by cardiovascular alterations, predominantly ascending aortic aneurysms. Although neurovascular complications are uncommon in MFS, the improvement in Marfan patients' life expectancy is revealing other secondary alterations, potentially including neurovascular disorders. However, little is known about small-vessel pathophysiology in MFS. MFS is associated with hyperactivated transforming growth factor (TGF)-β signaling, which among numerous other downstream effectors, induces the NADPH oxidase 4 (Nox4) isoform of NADPH oxidase, a strong enzymatic source of H2O2 We hypothesized that MFS induces middle cerebral artery (MCA) alterations and that Nox4 contributes to them. MCA properties from 3-, 6-, or 9-mo-old Marfan (Fbn1(C1039G/+)) mice were compared with those from age/sex-matched wild-type littermates. At 6 mo, Marfan compared with wild-type mice developed higher MCA wall/lumen (wild-type: 0.081 ± 0.004; Marfan: 0.093 ± 0.002; 60 mmHg; P < 0.05), coupled with increased reactive oxygen species production, TGF-β, and Nox4 expression. However, wall stiffness and myogenic autoregulation did not change. To investigate the influence of Nox4 on cerebrovascular properties, we generated Marfan mice with Nox4 deficiency (Nox4(-/-)). Strikingly, Nox4 deletion in Marfan mice aggravated MCA wall thickening (cross-sectional area; Marfan: 6,660 ± 363 μm(2); Marfan Nox4(-/-): 8,795 ± 824 μm(2); 60 mmHg; P < 0.05), accompanied by decreased TGF-β expression and increased collagen deposition and Nox1 expression. These findings provide the first evidence that Nox4 mitigates cerebral artery structural changes in a murine model of MFS.American Physiological Society2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/102549Articles publicats en revistes (Biomedicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaIngléshttp://dx.doi.org/10.1152/ajpheart.00770.2015American Journal of Physiology-Heart and Circulatory Physiology, 2016, vol. 310, num. 9, p. H1081-H1090http://dx.doi.org/10.1152/ajpheart.00770.2015(c) American Physiological Society, 2016info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1025492026-05-27T06:46:51Z
dc.title.none.fl_str_mv NADPH oxidase 4 attenuates cerebral artery changes during the progression of Marfan syndrome
title NADPH oxidase 4 attenuates cerebral artery changes during the progression of Marfan syndrome
spellingShingle NADPH oxidase 4 attenuates cerebral artery changes during the progression of Marfan syndrome
Onetti, Yara
Teixit connectiu
Malalties hereditàries
Aneurismes aòrtics
Factors de creixement
Connective tissue
Genetic diseases
Aortic aneurysms
Growth factors
title_short NADPH oxidase 4 attenuates cerebral artery changes during the progression of Marfan syndrome
title_full NADPH oxidase 4 attenuates cerebral artery changes during the progression of Marfan syndrome
title_fullStr NADPH oxidase 4 attenuates cerebral artery changes during the progression of Marfan syndrome
title_full_unstemmed NADPH oxidase 4 attenuates cerebral artery changes during the progression of Marfan syndrome
title_sort NADPH oxidase 4 attenuates cerebral artery changes during the progression of Marfan syndrome
dc.creator.none.fl_str_mv Onetti, Yara
Meirelles, Thayna
Dantas, Ana Paula
Schröder, Katrin
Vila, Elisabet
Egea Guri, Gustavo
Jiménez Altayó, Francesc
author Onetti, Yara
author_facet Onetti, Yara
Meirelles, Thayna
Dantas, Ana Paula
Schröder, Katrin
Vila, Elisabet
Egea Guri, Gustavo
Jiménez Altayó, Francesc
author_role author
author2 Meirelles, Thayna
Dantas, Ana Paula
Schröder, Katrin
Vila, Elisabet
Egea Guri, Gustavo
Jiménez Altayó, Francesc
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Teixit connectiu
Malalties hereditàries
Aneurismes aòrtics
Factors de creixement
Connective tissue
Genetic diseases
Aortic aneurysms
Growth factors
topic Teixit connectiu
Malalties hereditàries
Aneurismes aòrtics
Factors de creixement
Connective tissue
Genetic diseases
Aortic aneurysms
Growth factors
description Marfan syndrome (MFS) is a connective tissue disorder that is often associated with the fibrillin-1 (Fbn1) gene mutation and characterized by cardiovascular alterations, predominantly ascending aortic aneurysms. Although neurovascular complications are uncommon in MFS, the improvement in Marfan patients' life expectancy is revealing other secondary alterations, potentially including neurovascular disorders. However, little is known about small-vessel pathophysiology in MFS. MFS is associated with hyperactivated transforming growth factor (TGF)-β signaling, which among numerous other downstream effectors, induces the NADPH oxidase 4 (Nox4) isoform of NADPH oxidase, a strong enzymatic source of H2O2 We hypothesized that MFS induces middle cerebral artery (MCA) alterations and that Nox4 contributes to them. MCA properties from 3-, 6-, or 9-mo-old Marfan (Fbn1(C1039G/+)) mice were compared with those from age/sex-matched wild-type littermates. At 6 mo, Marfan compared with wild-type mice developed higher MCA wall/lumen (wild-type: 0.081 ± 0.004; Marfan: 0.093 ± 0.002; 60 mmHg; P < 0.05), coupled with increased reactive oxygen species production, TGF-β, and Nox4 expression. However, wall stiffness and myogenic autoregulation did not change. To investigate the influence of Nox4 on cerebrovascular properties, we generated Marfan mice with Nox4 deficiency (Nox4(-/-)). Strikingly, Nox4 deletion in Marfan mice aggravated MCA wall thickening (cross-sectional area; Marfan: 6,660 ± 363 μm(2); Marfan Nox4(-/-): 8,795 ± 824 μm(2); 60 mmHg; P < 0.05), accompanied by decreased TGF-β expression and increased collagen deposition and Nox1 expression. These findings provide the first evidence that Nox4 mitigates cerebral artery structural changes in a murine model of MFS.
publishDate 2016
dc.date.none.fl_str_mv 2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/102549
url https://hdl.handle.net/2445/102549
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1152/ajpheart.00770.2015
American Journal of Physiology-Heart and Circulatory Physiology, 2016, vol. 310, num. 9, p. H1081-H1090
http://dx.doi.org/10.1152/ajpheart.00770.2015
dc.rights.none.fl_str_mv (c) American Physiological Society, 2016
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Physiological Society, 2016
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Physiological Society
publisher.none.fl_str_mv American Physiological Society
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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