Association of circulating microRNAs with coronary artery disease and usefulness for reclassification of healthy individuals: the REGICOR Study

Dégano, Irene R.; Camps-Vilaró, Anna; Subirana Cachinero, Isaac; García-Mateo, Nadia; Cidad, Pilar; Muñoz Aguayo, Daniel; Puigdecanet Riubugent, Eulàlia; Nonell Mazelon, Lara, 1972-; Vila, Joan; Crepaldi, Felipe M.; Gonzalo-Calvo, David de; Llorente-Cortés, Vicenta; Pérez García, María Teresa; Elosua Llanos, Roberto; Fitó Colomer, Montserrat; Marrugat de la Iglesia, Jaume

Association of circulating microRNAs with coronary artery disease and usefulness for reclassification of healthy individuals: the REGICOR Study

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dc.contributor.author Dégano, Irene R.
dc.contributor.author Camps-Vilaró, Anna
dc.contributor.author Subirana Cachinero, Isaac
dc.contributor.author García-Mateo, Nadia
dc.contributor.author Cidad, Pilar
dc.contributor.author Muñoz Aguayo, Daniel
dc.contributor.author Puigdecanet Riubugent, Eulàlia
dc.contributor.author Nonell Mazelon, Lara, 1972-
dc.contributor.author Vila, Joan
dc.contributor.author Crepaldi, Felipe M.
dc.contributor.author Gonzalo-Calvo, David de
dc.contributor.author Llorente-Cortés, Vicenta
dc.contributor.author Pérez García, María Teresa
dc.contributor.author Elosua Llanos, Roberto
dc.contributor.author Fitó Colomer, Montserrat
dc.contributor.author Marrugat de la Iglesia, Jaume
dc.date.accessioned 2020-09-23T08:20:45Z
dc.date.available 2020-09-23T08:20:45Z
dc.date.issued 2020
dc.description.abstract Risk prediction tools cannot identify most individuals at high coronary artery disease (CAD) risk. Oxidized low-density lipoproteins (oxLDLs) and microRNAs are actively involved in atherosclerosis. Our aim was to examine the association of CAD and oxLDLs-induced microRNAs, and to assess the microRNAs predictive capacity of future CAD events. Human endothelial and vascular smooth muscle cells were treated with oxidized/native low-density lipoproteins, and microRNA expression was analyzed. Differentially expressed and CAD-related miRNAs were examined in serum samples from (1) a case-control study with 476 myocardial infarction (MI) patients and 487 controls, and (2) a case-cohort study with 105 incident CAD cases and 455 randomly-selected cohort participants. MicroRNA expression was analyzed with custom OpenArray plates, log rank tests and Cox regression models. Twenty-one microRNAs, two previously undescribed (hsa-miR-193b-5p and hsa-miR-1229-5p), were up- or down-regulated upon cell treatment with oxLDLs. One of the 21, hsa-miR-122-5p, was also upregulated in MI cases (fold change = 4.85). Of the 28 CAD-related microRNAs tested, 11 were upregulated in MI cases -1 previously undescribed (hsa-miR-16-5p)-, and 1/11 was also associated with CAD incidence (adjusted hazard ratio = 0.55 (0.35-0.88)) and improved CAD risk reclassification, hsa-miR-143-3p. We identified 2 novel microRNAs modulated by oxLDLs in endothelial cells, 1 novel microRNA upregulated in AMI cases compared to controls, and one circulating microRNA that improved CAD risk classification.
dc.description.sponsorship This work was supported by the Spain’s Ministry of Science and Innovation (Madrid, Spain), co-financed with European Union European Regional Development Funds –ERDF- (FIS-CP12/03287, FIS-14/00449, FIS-PI081327, INTRASALUD PI11/01801, PI15/00064, IJCI-2016-29393 to DdG-C, CIBERCV (CB16/11/00229, 00246, 00403), CIBERESP CB06/02/0029, CIBEROBN CB06/03/0028); the Spain’s ministry of Economy and Competiveness (Madrid, Spain) (BFU2016-75360-R); the BBVA Foundation (Bilbao, Spain) (PR-16-BIO-CAR-0041); the Health Departament of the Generalitat de Catalunya (Barcelona, Spain) through the Agència de Gestió d’Ajuts Universitaris de Recerca de Catalunya (AGAUR) (Barcelona, Spain) (2017SGR222), the Strategic Plan for research and health innovation (PERIS) (Barcelona, Spain) (SLT006/17/00234, SLT002/16/00145, SLT006/17/00029 to IRD); and by the Junta de Castilla y León (Valladolid, Spain) (VA114P17). CIBERs of Pathophysiology of Obesity and Nutrition (CIBEROBN), Cardiovascular Diseases (CIBERCV), and Epidemiology (CIBERESP) are initiatives of the Instituto de Salud Carlos III, Madrid, Spain.
dc.format.mimetype application/pdf
dc.identifier.citation Dégano IR, Camps-Vilaró A, Subirana I, García-Mateo N, Cidad P, Muñoz-Aguayo D. et al. Association of circulating microRNAs with coronary artery disease and usefulness for reclassification of healthy individuals: the REGICOR Study. J Clin Med. 2020 May 9; 9(5):1402. DOI: 10.3390/jcm9051402
dc.identifier.doi http://dx.doi.org/10.3390/jcm9051402
dc.identifier.issn 2077-0383
dc.identifier.uri http://hdl.handle.net/10230/45333
dc.language.iso eng
dc.publisher MDPI
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2016-75360-R
dc.rights © 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/).
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword Circulating biomarkers
dc.subject.keyword Coronary artery disease
dc.subject.keyword MicroRNAs
dc.subject.keyword Myocardial infarction
dc.subject.keyword Oxidized low-density lipoproteins
dc.title Association of circulating microRNAs with coronary artery disease and usefulness for reclassification of healthy individuals: the REGICOR Study
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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