{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T17:30:40Z","timestamp":1793813440760,"version":"4.6.1"},"reference-count":47,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T00:00:00Z","timestamp":1622764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Tumor necrosis factor alpha (TNF-\u03b1) is proatherogenic and associated with the risk of acute ischemic events, although the mechanisms that regulate TNF-\u03b1 expression in stable coronary artery disease (SCAD) are not fully understood. We investigated whether metabolic, inflammatory, and epigenetic (microRNA (miRNA)) markers are associated with TNF-\u03b1 expression in SCAD. Materials and Methods: Patients with SCAD were prospectively recruited and their metabolic and inflammatory profiles were assessed. TNF-\u03b1 levels were assessed using an enzyme-linked immunosorbent assay. The relative expression of six circulating miRNAs associated with the regulation of inflammation and\/or atherosclerosis was determined. Results: Of the 24 included patients with the mean age of 65 (9) years, 88% were male, and 54% were diabetic. The TNF-\u03b1 levels were (median (interquartile range)) 1.0 (0.7\u20131.1) pg\/mL. The percentage of glycosylated hemoglobin (r = 0.418, p = 0.042), serum triglyceride levels (r = 0.429, p = 0.037), and C-reactive protein levels (r = 0.407, p = 0.048) were positively correlated with TNF-\u03b1 levels. Of the candidate miRNAs, miR-146a expression levels were negatively correlated with TNF-\u03b1 levels (as indicated by r = 0.500, p = 0.035 for correlation between delta cycle threshold (\u0394Ct) miR-146a and TNF-\u03b1 levels). In multivariate analysis, serum triglyceride levels and miR-146a expression levels were independently associated with TNF-\u03b1 levels. miR-146 expression levels were not associated with metabolic or other inflammatory parameters and were negatively correlated with the number of coronary vessels with obstructive disease (as indicated by r = 0.556, p = 0.017 for correlation between \u0394Ct miR-146a and number of diseased vessels). Conclusions: miR-146a expression levels were negatively correlated with TNF-\u03b1 levels in patients with SCAD, irrespective of other metabolic or inflammatory markers, and with the severity of coronary artery disease. The results add to the knowledge on the role of miR-146a in TNF-\u03b1-based inflammation in SCAD and support future research on the potential therapeutic use of miR-146a in such a clinical scenario.<\/jats:p>","DOI":"10.3390\/medicina57060575","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T11:12:13Z","timestamp":1622805133000},"page":"575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Association between miR-146a and Tumor Necrosis Factor Alpha (TNF-\u03b1) in Stable Coronary Artery Disease"],"prefix":"10.3390","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0467-2608","authenticated-orcid":false,"given":"Tiago","family":"Pereira-da-Silva","sequence":"first","affiliation":[{"name":"Department of Cardiology, Hospital de Santa Marta, Centro Hospitalar Universit\u00e1rio de Lisboa Central, 1169-024 Lisbon, Portugal"},{"name":"NOVA Doctoral School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia","family":"Napole\u00e3o","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Universidade de Lisboa, 1649-028 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9020-7539","authenticated-orcid":false,"given":"Marina C.","family":"Costa","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Universidade de Lisboa, 1649-028 Lisbon, Portugal"},{"name":"Cardiomics Unit, Centro Cardiovascular da Universidade de Lisboa, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6565-1600","authenticated-orcid":false,"given":"Andr\u00e9 F.","family":"Gabriel","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Universidade de Lisboa, 1649-028 Lisbon, Portugal"},{"name":"Cardiomics Unit, Centro Cardiovascular da Universidade de Lisboa, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mafalda","family":"Selas","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital de Santa Marta, Centro Hospitalar Universit\u00e1rio de Lisboa Central, 1169-024 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filipa","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital de Santa Marta, Centro Hospitalar Universit\u00e1rio de Lisboa Central, 1169-024 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8072-8557","authenticated-orcid":false,"given":"Francisco J.","family":"Enguita","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Universidade de Lisboa, 1649-028 Lisbon, Portugal"},{"name":"Cardiomics Unit, Centro Cardiovascular da Universidade de Lisboa, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Cruz Ferreira","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital de Santa Marta, Centro Hospitalar Universit\u00e1rio de Lisboa Central, 1169-024 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Mota Carmo","sequence":"additional","affiliation":[{"name":"Chronic Diseases Research Center (CEDOC), NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1150-082 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e139","DOI":"10.1161\/CIR.0000000000000757","article-title":"Heart disease and stroke statistics-2020 update: A report from the American Heart Association","volume":"141","author":"Virani","year":"2020","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1016\/j.jacc.2009.09.009","article-title":"Inflammation in atherosclerosis: From pathophysiology to practice","volume":"54","author":"Libby","year":"2009","journal-title":"J. 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