BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque
dc.contributor.author | Alloza Moral, Iraide | |
dc.contributor.author | Salegi, Andrea | |
dc.contributor.author | Mena Lucía, Jorge | |
dc.contributor.author | Tulloch Navarro, Raquel | |
dc.contributor.author | Martín Plágaro, César Augusto | |
dc.contributor.author | Aspichueta Celaá, Patricia | |
dc.contributor.author | Martínez Salazar, Lucía | |
dc.contributor.author | Uriarte Carpio, Jon | |
dc.contributor.author | De la Hera Cagigal, Patricia | |
dc.contributor.author | Vega Manrique, Reyes | |
dc.contributor.author | Triviño, Juan Carlos | |
dc.contributor.author | Freijo, María del Mar | |
dc.contributor.author | Vandenbroeck, Koen | |
dc.date.accessioned | 2021-01-13T09:13:18Z | |
dc.date.available | 2021-01-13T09:13:18Z | |
dc.date.issued | 2020-12-09 | |
dc.identifier.citation | International Journal of Molecular Sciences 21(24) : (2020) // Article ID9387 | es_ES |
dc.identifier.issn | 1422-0067 | |
dc.identifier.uri | http://hdl.handle.net/10810/49724 | |
dc.description.abstract | 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. | es_ES |
dc.description.sponsorship | 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. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | |
dc.subject | atherosclerosis | es_ES |
dc.subject | carotid plaque | es_ES |
dc.subject | BIRC6 | es_ES |
dc.subject | autophagy | es_ES |
dc.subject | red cell distribution width | es_ES |
dc.subject | stroke | es_ES |
dc.title | BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.date.updated | 2020-12-24T15:57:15Z | |
dc.rights.holder | 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/). | es_ES |
dc.relation.publisherversion | https://www.mdpi.com/1422-0067/21/24/9387/htm | es_ES |
dc.identifier.doi | 10.3390/ijms21249387 | |
dc.departamentoes | Bioquímica y biología molecular | |
dc.departamentoes | Fisiología | |
dc.departamentoeu | Biokimika eta biologia molekularra | |
dc.departamentoeu | Fisiologia |
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Except where otherwise noted, this item's license is described as 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/).