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Open AccessArticle

Association of Circulating microRNAs with Coronary Artery Disease and Usefulness for Reclassification of Healthy Individuals: The REGICOR Study

1
REGICOR Study Group, IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain
2
CIBER of Cardiovascular Diseases (CIBERCV), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
3
Faculty of Medicine, University of Vic-Central University of Catalonia (UVic-UCC), 08500 Vic, Spain
4
CIBER Epidemiology and Public Health, ISCIII, 28029 Madrid, Spain
5
Departamento de Bioquímica y Biología Molecular y Fisiología and Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and Consejo Superior de Investigaciones Científicas (CSIC), 47003 Valladolid, Spain
6
Cardiovascular Risk and nutrition Group, IMIM, 08003 Barcelona, Spain
7
CIBER of Obesity and Nutrition (CIBEROBN), ISCIII, 28029 Madrid, Spain
8
MARGenomics, IMIM, 08003 Barcelona, Spain
9
Biomedical Research Institute SanPau (IIB Sant Pau), 08041 Barcelona, Spain
10
Institute of Biomedical Research of Barcelona (IIBB)–Spanish National Research Council (CSIC), 08036 Barcelona, Spain
11
Cardiovascular Epidemiology and Genetics Group, IMIM, 08003 Barcelona, Spain
*
Authors to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(5), 1402; https://doi.org/10.3390/jcm9051402
Received: 31 March 2020 / Revised: 2 May 2020 / Accepted: 4 May 2020 / Published: 9 May 2020
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. View Full-Text
Keywords: oxidized low-density lipoproteins; microRNAs; myocardial infarction; coronary artery disease; circulating biomarkers oxidized low-density lipoproteins; microRNAs; myocardial infarction; coronary artery disease; circulating biomarkers
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MDPI and ACS Style

Dégano, I.R.; Camps-Vilaró, A.; Subirana, I.; García-Mateo, N.; Cidad, P.; Muñoz-Aguayo, D.; Puigdecanet, E.; Nonell, L.; Vila, J.; Crepaldi, F.M.; de Gonzalo-Calvo, D.; Llorente-Cortés, V.; Pérez-García, M.T.; Elosua, R.; Fitó, M.; Marrugat, J. Association of Circulating microRNAs with Coronary Artery Disease and Usefulness for Reclassification of Healthy Individuals: The REGICOR Study. J. Clin. Med. 2020, 9, 1402.

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