DNA methylation of MMPs and TIMPs in atherothrombosis process in carotid plaques and blood tissues

Background and purpose: polymorphisms and serum levels of Matrix Metalloproteinases (MMP) and Tissue Inhibitor of Metalloproteinases (TIMP) have been studied with regard to atheromatous plaques and ischemic stroke, while no studies of DNA methylation (DNAm) patterns of MMP or TIMP have been performe...

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Autores: Gallego Fàbrega, Cristina, Cullell, Natalia, Soriano Tarraga, Carolina, Carrera, Caty, Torres Águila, Nuria Paz, Muiño Acuña, Elena, Cárcel Márquez, Jara, Castro de Moura, Manuel, Fernández Sanles, Alba, Esteller, Manel, Elosua, Roberto, Jiménez Conde, Jordi, Roquer, Jaume, Montaner, Joan, Krupinski, Jerzy, Fernández Cadenas, Israel
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:2445/178604
Acceso en línea:https://hdl.handle.net/2445/178604
Access Level:acceso abierto
Palabra clave:ADN
Metilació
Epigenètica
Metal·loproteïnases
DNA
Methylation
Epigenetics
Metalloproteinases
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spelling DNA methylation of MMPs and TIMPs in atherothrombosis process in carotid plaques and blood tissuesGallego Fàbrega, CristinaCullell, NataliaSoriano Tarraga, CarolinaCarrera, CatyTorres Águila, Nuria PazMuiño Acuña, ElenaCárcel Márquez, JaraCastro de Moura, ManuelFernández Sanles, AlbaEsteller, ManelElosua, RobertoJiménez Conde, JordiRoquer, JaumeMontaner, JoanKrupinski, JerzyFernández Cadenas, IsraelADNMetilacióEpigenèticaMetal·loproteïnasesDNAMethylationEpigeneticsMetalloproteinasesBackground and purpose: polymorphisms and serum levels of Matrix Metalloproteinases (MMP) and Tissue Inhibitor of Metalloproteinases (TIMP) have been studied with regard to atheromatous plaques and ischemic stroke, while no studies of DNA methylation (DNAm) patterns of MMP or TIMP have been performed to that end. Here, we evaluate DNAm levels of the MMP and TIMP gene families in human carotid plaques and blood samples of atherothrombotic stroke patients. Methods: we profiled the DNAm status of stable and ulcerated atherosclerotic plaques obtained as pair sets from three patients who underwent carotid endarterectomy surgery. We selected 415 CpG sites, mapping into MMPs and TIMPs genes for further study. Secondly, the statistically associated CpG sites were analyzed in blood samples from two separate atherothrombotic stroke cohorts (total sample size = 307), ischemic stroke-cohort 1 (ISC-1): 37 atherothrombotic patients and 6 controls, ischemic stroke-cohort 2 (ISC-2): 80 atherothrombotic patients and 184 controls. DNAm levels from plaque tissue and blood samples were evaluated using a high-density microarray Infinium, HumanMethylation450 BeadChip and Infinium MethylationEPIC BeadChip. Results: three CpG sites were statistically significantly associated with unstable plaque portions; cg02969624, q-value = 0.035 (TIMP2), and cg04316754, q-value = 0.037 (MMP24) were hypermethylated, while cg24211657 q-value = 0.035 (TIMP2) was hypomethylated. Association of cg04316754 (MMP24) methylation levels with atherothrombotic risk was also observed in blood tissue: ISC-1 p-values = 0.03, ISC-2 p-value = 1.9 × 10-04. Conclusions: the results suggest different DNAm status of MMP24 between stable and unstable atherothrombotic carotid plaques, and between atherothrombotic stroke and controls in blood samples.Impact Journals2021202120202021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion8 p.application/pdfhttps://hdl.handle.net/2445/178604Articles publicats en revistes (Ciències Fisiològiques)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/10.18632/oncotarget.27469Oncotarget, 2020, vol. 11, num. 10, p. 905-912https://doi.org/10.18632/oncotarget.27469cc-by (c) Gallego Fàbrega, Cristina et al., 2020https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1786042026-05-29T05:05:01Z
dc.title.none.fl_str_mv DNA methylation of MMPs and TIMPs in atherothrombosis process in carotid plaques and blood tissues
title DNA methylation of MMPs and TIMPs in atherothrombosis process in carotid plaques and blood tissues
spellingShingle DNA methylation of MMPs and TIMPs in atherothrombosis process in carotid plaques and blood tissues
Gallego Fàbrega, Cristina
ADN
Metilació
Epigenètica
Metal·loproteïnases
DNA
Methylation
Epigenetics
Metalloproteinases
title_short DNA methylation of MMPs and TIMPs in atherothrombosis process in carotid plaques and blood tissues
title_full DNA methylation of MMPs and TIMPs in atherothrombosis process in carotid plaques and blood tissues
title_fullStr DNA methylation of MMPs and TIMPs in atherothrombosis process in carotid plaques and blood tissues
title_full_unstemmed DNA methylation of MMPs and TIMPs in atherothrombosis process in carotid plaques and blood tissues
title_sort DNA methylation of MMPs and TIMPs in atherothrombosis process in carotid plaques and blood tissues
dc.creator.none.fl_str_mv Gallego Fàbrega, Cristina
Cullell, Natalia
Soriano Tarraga, Carolina
Carrera, Caty
Torres Águila, Nuria Paz
Muiño Acuña, Elena
Cárcel Márquez, Jara
Castro de Moura, Manuel
Fernández Sanles, Alba
Esteller, Manel
Elosua, Roberto
Jiménez Conde, Jordi
Roquer, Jaume
Montaner, Joan
Krupinski, Jerzy
Fernández Cadenas, Israel
author Gallego Fàbrega, Cristina
author_facet Gallego Fàbrega, Cristina
Cullell, Natalia
Soriano Tarraga, Carolina
Carrera, Caty
Torres Águila, Nuria Paz
Muiño Acuña, Elena
Cárcel Márquez, Jara
Castro de Moura, Manuel
Fernández Sanles, Alba
Esteller, Manel
Elosua, Roberto
Jiménez Conde, Jordi
Roquer, Jaume
Montaner, Joan
Krupinski, Jerzy
Fernández Cadenas, Israel
author_role author
author2 Cullell, Natalia
Soriano Tarraga, Carolina
Carrera, Caty
Torres Águila, Nuria Paz
Muiño Acuña, Elena
Cárcel Márquez, Jara
Castro de Moura, Manuel
Fernández Sanles, Alba
Esteller, Manel
Elosua, Roberto
Jiménez Conde, Jordi
Roquer, Jaume
Montaner, Joan
Krupinski, Jerzy
Fernández Cadenas, Israel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ADN
Metilació
Epigenètica
Metal·loproteïnases
DNA
Methylation
Epigenetics
Metalloproteinases
topic ADN
Metilació
Epigenètica
Metal·loproteïnases
DNA
Methylation
Epigenetics
Metalloproteinases
description Background and purpose: polymorphisms and serum levels of Matrix Metalloproteinases (MMP) and Tissue Inhibitor of Metalloproteinases (TIMP) have been studied with regard to atheromatous plaques and ischemic stroke, while no studies of DNA methylation (DNAm) patterns of MMP or TIMP have been performed to that end. Here, we evaluate DNAm levels of the MMP and TIMP gene families in human carotid plaques and blood samples of atherothrombotic stroke patients. Methods: we profiled the DNAm status of stable and ulcerated atherosclerotic plaques obtained as pair sets from three patients who underwent carotid endarterectomy surgery. We selected 415 CpG sites, mapping into MMPs and TIMPs genes for further study. Secondly, the statistically associated CpG sites were analyzed in blood samples from two separate atherothrombotic stroke cohorts (total sample size = 307), ischemic stroke-cohort 1 (ISC-1): 37 atherothrombotic patients and 6 controls, ischemic stroke-cohort 2 (ISC-2): 80 atherothrombotic patients and 184 controls. DNAm levels from plaque tissue and blood samples were evaluated using a high-density microarray Infinium, HumanMethylation450 BeadChip and Infinium MethylationEPIC BeadChip. Results: three CpG sites were statistically significantly associated with unstable plaque portions; cg02969624, q-value = 0.035 (TIMP2), and cg04316754, q-value = 0.037 (MMP24) were hypermethylated, while cg24211657 q-value = 0.035 (TIMP2) was hypomethylated. Association of cg04316754 (MMP24) methylation levels with atherothrombotic risk was also observed in blood tissue: ISC-1 p-values = 0.03, ISC-2 p-value = 1.9 × 10-04. Conclusions: the results suggest different DNAm status of MMP24 between stable and unstable atherothrombotic carotid plaques, and between atherothrombotic stroke and controls in blood samples.
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/2445/178604
url https://hdl.handle.net/2445/178604
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/10.18632/oncotarget.27469
Oncotarget, 2020, vol. 11, num. 10, p. 905-912
https://doi.org/10.18632/oncotarget.27469
dc.rights.none.fl_str_mv cc-by (c) Gallego Fàbrega, Cristina et al., 2020
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Gallego Fàbrega, Cristina et al., 2020
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 8 p.
application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
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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score 15,811543

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