BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque

Carotid atherosclerotic plaque rupture can lead to cerebrovascular accident (CVA). By comparing RNA-Seq data from vascular smooth muscle cells (VSMC) extracted from carotid atheroma surgically excised from a group of asymptomatic and symptomatic subjects, we identified more than 700 genomic variants...

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Autores: Alloza Moral, Iraide, Salegi, Andrea, Mena Lucía, Jorge, Tulloch Navarro, Raquel, Martín Plágaro, César Augusto, Aspichueta Celaá, Patricia, Martínez Salazar, Lucía, Uriarte Carpio, Jon, De la Hera Cagigal, Patricia, Vega Manrique, Reyes, Triviño, Juan Carlos, Freijo, María del Mar, Vandenbroeck, Koen
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/49724
Acceso en línea:http://hdl.handle.net/10810/49724
Access Level:acceso abierto
Palabra clave:atherosclerosis
carotid plaque
BIRC6
autophagy
red cell distribution width
stroke
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spelling BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic PlaqueAlloza Moral, IraideSalegi, AndreaMena Lucía, JorgeTulloch Navarro, RaquelMartín Plágaro, César AugustoAspichueta Celaá, PatriciaMartínez Salazar, LucíaUriarte Carpio, JonDe la Hera Cagigal, PatriciaVega Manrique, ReyesTriviño, Juan CarlosFreijo, María del MarVandenbroeck, Koenatherosclerosiscarotid plaqueBIRC6autophagyred cell distribution widthstrokeCarotid atherosclerotic plaque rupture can lead to cerebrovascular accident (CVA). By comparing RNA-Seq data from vascular smooth muscle cells (VSMC) extracted from carotid atheroma surgically excised from a group of asymptomatic and symptomatic subjects, we identified more than 700 genomic variants associated with symptomatology (p < 0.05). From these, twelve single nucleotide polymorphisms (SNPs) were selected for further validation. Comparing genotypes of a hospital-based cohort of asymptomatic with symptomatic patients, an exonic SNP in the BIRC6 (BRUCE/Apollon) gene, rs35286811, emerged as significantly associated with CVA symptomatology (p = 0.002; OR = 2.24). Moreover, BIRC6 mRNA levels were significantly higher in symptomatic than asymptomatic subjects upon measurement by qPCR in excised carotid atherosclerotic tissue (p < 0.0001), and significantly higher in carriers of the rs35286811 risk allele (p < 0.0001). rs35286811 is a proxy of a GWAS SNP reported to be associated with red cell distribution width (RDW); RDW was increased in symptomatic patients (p < 0.03), but was not influenced by the rs35286811 genotype in our cohort. BIRC6 is a negative regulator of both apoptosis and autophagy. This work introduces BIRC6 as a novel genetic risk factor for stroke, and identifies autophagy as a genetically regulated mechanism of carotid plaque vulnerability.This work was financially supported by grants from the Departments of Education (Ref. PIBA2018-67) and Health (Ref. RIS3-2019222038) of the Basque Government, Vitoria-Gasteiz, Spain; by the Spanish Neurovascular Network (INVICTUSplus) (Ref. RD16/0019/0007) funded by the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Madrid, Spain; and by the research project grant (IKERIKTUS) funded by the RefbioII Trans-Pyrenean Cooperation Network for Biomedical Research financed by Horizon 2020. I.A. is supported by the Maratón EiTB 2017 for Funding of Research into Stroke, Bilbao, Spain (Ref. BIO18/IC/005); R.T.N. is the recipient of a fellowship from the Secretaría Nacional de Ciencia y Tecnología e Innovación (SENACYT; Convocatoria Doctorado de Investigación Ronda III, 2018; Ref. BIDP-III-2018-12) of the Gobierno Nacional, República de Panamá.MDPI2021202120202020info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/49724reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoIngléshttps://www.mdpi.com/1422-0067/21/24/9387/htminfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/3.0/es/2020 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/).oai:addi.ehu.eus:10810/497242026-06-18T09:23:17Z
dc.title.none.fl_str_mv BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque
title BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque
spellingShingle BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque
Alloza Moral, Iraide
atherosclerosis
carotid plaque
BIRC6
autophagy
red cell distribution width
stroke
title_short BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque
title_full BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque
title_fullStr BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque
title_full_unstemmed BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque
title_sort BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque
dc.creator.none.fl_str_mv Alloza Moral, Iraide
Salegi, Andrea
Mena Lucía, Jorge
Tulloch Navarro, Raquel
Martín Plágaro, César Augusto
Aspichueta Celaá, Patricia
Martínez Salazar, Lucía
Uriarte Carpio, Jon
De la Hera Cagigal, Patricia
Vega Manrique, Reyes
Triviño, Juan Carlos
Freijo, María del Mar
Vandenbroeck, Koen
author Alloza Moral, Iraide
author_facet Alloza Moral, Iraide
Salegi, Andrea
Mena Lucía, Jorge
Tulloch Navarro, Raquel
Martín Plágaro, César Augusto
Aspichueta Celaá, Patricia
Martínez Salazar, Lucía
Uriarte Carpio, Jon
De la Hera Cagigal, Patricia
Vega Manrique, Reyes
Triviño, Juan Carlos
Freijo, María del Mar
Vandenbroeck, Koen
author_role author
author2 Salegi, Andrea
Mena Lucía, Jorge
Tulloch Navarro, Raquel
Martín Plágaro, César Augusto
Aspichueta Celaá, Patricia
Martínez Salazar, Lucía
Uriarte Carpio, Jon
De la Hera Cagigal, Patricia
Vega Manrique, Reyes
Triviño, Juan Carlos
Freijo, María del Mar
Vandenbroeck, Koen
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv atherosclerosis
carotid plaque
BIRC6
autophagy
red cell distribution width
stroke
topic atherosclerosis
carotid plaque
BIRC6
autophagy
red cell distribution width
stroke
description Carotid atherosclerotic plaque rupture can lead to cerebrovascular accident (CVA). By comparing RNA-Seq data from vascular smooth muscle cells (VSMC) extracted from carotid atheroma surgically excised from a group of asymptomatic and symptomatic subjects, we identified more than 700 genomic variants associated with symptomatology (p < 0.05). From these, twelve single nucleotide polymorphisms (SNPs) were selected for further validation. Comparing genotypes of a hospital-based cohort of asymptomatic with symptomatic patients, an exonic SNP in the BIRC6 (BRUCE/Apollon) gene, rs35286811, emerged as significantly associated with CVA symptomatology (p = 0.002; OR = 2.24). Moreover, BIRC6 mRNA levels were significantly higher in symptomatic than asymptomatic subjects upon measurement by qPCR in excised carotid atherosclerotic tissue (p < 0.0001), and significantly higher in carriers of the rs35286811 risk allele (p < 0.0001). rs35286811 is a proxy of a GWAS SNP reported to be associated with red cell distribution width (RDW); RDW was increased in symptomatic patients (p < 0.03), but was not influenced by the rs35286811 genotype in our cohort. BIRC6 is a negative regulator of both apoptosis and autophagy. This work introduces BIRC6 as a novel genetic risk factor for stroke, and identifies autophagy as a genetically regulated mechanism of carotid plaque vulnerability.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/49724
url http://hdl.handle.net/10810/49724
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://www.mdpi.com/1422-0067/21/24/9387/htm
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/3.0/es/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301603

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