New candidate blood biomarkers potentially associated with white matter hyperintensities progression

We aimed to discover blood biomarkers associated with longitudinal changes in white matter hyperintensities (WMH). This study was divided into a discovery phase and a replication phase. Subjects in both studies were patients with hypertension, aged 50-70, who underwent two magnetic resonance imaging...

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Autores: Jiménez-Balado, Joan|||0000-0003-4125-9134, Pizarro Gonzálvez, Jesús|||0000-0002-5808-9293, Riba Llena, Iolanda, Penalba, Anna, Faura, Júlia|||0000-0002-8436-1377, Palà, Elena|||0000-0002-1074-990X, Montaner, Joan|||0000-0003-4845-2279, Hernandez Guillamon, Maria Mar|||0000-0001-8844-0091, Delgado Martínez, María Pilar|||0000-0002-1628-4488
Formato: artículo
Fecha de publicación:2021
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:256503
Acesso em linha:https://ddd.uab.cat/record/256503
https://dx.doi.org/urn:doi:10.1038/s41598-021-93498-w
Access Level:acceso abierto
Palavra-chave:Neuroscience
Blood-brain barrier
Neuro-vascular interactions
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spelling New candidate blood biomarkers potentially associated with white matter hyperintensities progressionJiménez-Balado, Joan|||0000-0003-4125-9134Pizarro Gonzálvez, Jesús|||0000-0002-5808-9293Riba Llena, IolandaPenalba, AnnaFaura, Júlia|||0000-0002-8436-1377Palà, Elena|||0000-0002-1074-990XMontaner, Joan|||0000-0003-4845-2279Hernandez Guillamon, Maria Mar|||0000-0001-8844-0091Delgado Martínez, María Pilar|||0000-0002-1628-4488NeuroscienceBlood-brain barrierNeuro-vascular interactionsWe aimed to discover blood biomarkers associated with longitudinal changes in white matter hyperintensities (WMH). This study was divided into a discovery phase and a replication phase. Subjects in both studies were patients with hypertension, aged 50-70, who underwent two magnetic resonance imaging (MRI) sessions and blood extractions over a 4-year follow-up period. In the discovery phase, we screened 1305 proteins in 12 subjects with WMH progression and in 12 matched control subjects. We found that 41 proteins were differentially expressed: 13 were upregulated and 28 were downregulated. We subsequently selected three biomarkers for replication in baseline and follow-up samples in 80 subjects with WMH progression and in 80 control subjects. The selected protein candidates for the replication were MMP9 (matrix metalloproteinase-9), which was higher in cases, MET (hepatocyte growth factor receptor) and ASAH2 (neutral ceramidase), which were both lower in cases of WMH progression. Baseline biomarker concentrations did not predict WMH progression. In contrast, patients with WMH progression presented a steeper decline in MET over time. Furthermore, cases showed higher MMP9 and lower ASAH2 levels than controls at the follow-up. These results indicate that MMP9, MET, and ASAH2 are potentially associated with the progression of WMH, and could therefore be interesting candidates to validate in future studies.Universitat Autònoma de Barcelona 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/256503https://dx.doi.org/urn:doi:10.1038/s41598-021-93498-wreponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017_FI_B00064Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI14/01535Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17/02222Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 ICI14/307Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI19/00217Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CP15/00010Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 JR15/0003open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2565032026-06-06T12:50:31Z
dc.title.none.fl_str_mv New candidate blood biomarkers potentially associated with white matter hyperintensities progression
title New candidate blood biomarkers potentially associated with white matter hyperintensities progression
spellingShingle New candidate blood biomarkers potentially associated with white matter hyperintensities progression
Jiménez-Balado, Joan|||0000-0003-4125-9134
Neuroscience
Blood-brain barrier
Neuro-vascular interactions
title_short New candidate blood biomarkers potentially associated with white matter hyperintensities progression
title_full New candidate blood biomarkers potentially associated with white matter hyperintensities progression
title_fullStr New candidate blood biomarkers potentially associated with white matter hyperintensities progression
title_full_unstemmed New candidate blood biomarkers potentially associated with white matter hyperintensities progression
title_sort New candidate blood biomarkers potentially associated with white matter hyperintensities progression
dc.creator.none.fl_str_mv Jiménez-Balado, Joan|||0000-0003-4125-9134
Pizarro Gonzálvez, Jesús|||0000-0002-5808-9293
Riba Llena, Iolanda
Penalba, Anna
Faura, Júlia|||0000-0002-8436-1377
Palà, Elena|||0000-0002-1074-990X
Montaner, Joan|||0000-0003-4845-2279
Hernandez Guillamon, Maria Mar|||0000-0001-8844-0091
Delgado Martínez, María Pilar|||0000-0002-1628-4488
author Jiménez-Balado, Joan|||0000-0003-4125-9134
author_facet Jiménez-Balado, Joan|||0000-0003-4125-9134
Pizarro Gonzálvez, Jesús|||0000-0002-5808-9293
Riba Llena, Iolanda
Penalba, Anna
Faura, Júlia|||0000-0002-8436-1377
Palà, Elena|||0000-0002-1074-990X
Montaner, Joan|||0000-0003-4845-2279
Hernandez Guillamon, Maria Mar|||0000-0001-8844-0091
Delgado Martínez, María Pilar|||0000-0002-1628-4488
author_role author
author2 Pizarro Gonzálvez, Jesús|||0000-0002-5808-9293
Riba Llena, Iolanda
Penalba, Anna
Faura, Júlia|||0000-0002-8436-1377
Palà, Elena|||0000-0002-1074-990X
Montaner, Joan|||0000-0003-4845-2279
Hernandez Guillamon, Maria Mar|||0000-0001-8844-0091
Delgado Martínez, María Pilar|||0000-0002-1628-4488
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Neuroscience
Blood-brain barrier
Neuro-vascular interactions
topic Neuroscience
Blood-brain barrier
Neuro-vascular interactions
description We aimed to discover blood biomarkers associated with longitudinal changes in white matter hyperintensities (WMH). This study was divided into a discovery phase and a replication phase. Subjects in both studies were patients with hypertension, aged 50-70, who underwent two magnetic resonance imaging (MRI) sessions and blood extractions over a 4-year follow-up period. In the discovery phase, we screened 1305 proteins in 12 subjects with WMH progression and in 12 matched control subjects. We found that 41 proteins were differentially expressed: 13 were upregulated and 28 were downregulated. We subsequently selected three biomarkers for replication in baseline and follow-up samples in 80 subjects with WMH progression and in 80 control subjects. The selected protein candidates for the replication were MMP9 (matrix metalloproteinase-9), which was higher in cases, MET (hepatocyte growth factor receptor) and ASAH2 (neutral ceramidase), which were both lower in cases of WMH progression. Baseline biomarker concentrations did not predict WMH progression. In contrast, patients with WMH progression presented a steeper decline in MET over time. Furthermore, cases showed higher MMP9 and lower ASAH2 levels than controls at the follow-up. These results indicate that MMP9, MET, and ASAH2 are potentially associated with the progression of WMH, and could therefore be interesting candidates to validate in future studies.
publishDate 2021
dc.date.none.fl_str_mv 2
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/256503
https://dx.doi.org/urn:doi:10.1038/s41598-021-93498-w
url https://ddd.uab.cat/record/256503
https://dx.doi.org/urn:doi:10.1038/s41598-021-93498-w
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017_FI_B00064
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI14/01535
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17/02222
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 ICI14/307
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI19/00217
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CP15/00010
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 JR15/0003
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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