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Growing evidence supports the inflammation-driven calcification model, mediated by cytokines such as interferons (IFNs) and tumor necrosis factor (TNF)-\u03b1. Our goal was investigating IFNs\u2019 effects in human aortic valve endothelial cells (VEC) and the potential differences between aortic (aVEC) and ventricular (vVEC) side cells. The endothelial phenotype was analyzed by Western blot, qPCR, ELISA, monocyte adhesion, and migration assays. In mixed VEC populations, IFNs promoted the activation of signal transducers and activators of transcription-1 and nuclear factor-\u03baB, and the subsequent up-regulation of pro-inflammatory molecules. Side-specific VEC were activated with IFN-\u03b3 and TNF-\u03b1 in an orbital shaker flow system. TNF-\u03b1, but not IFN-\u03b3, induced hypoxia-inducible factor (HIF)-1\u03b1 stabilization or endothelial nitric oxide synthase downregulation. Additionally, IFN-\u03b3 inhibited TNF-\u03b1\u2013induced migration of aVEC. Also, IFN-\u03b3 triggered cytokine secretion and adhesion molecule expression in aVEC and vVEC. Finally, aVEC were more prone to cytokine-mediated monocyte adhesion under multiaxial flow conditions as compared with uniaxial flow. In conclusion, IFNs promote inflammation and reduce TNF-\u03b1\u2013mediated migration in human VEC. Moreover, monocyte adhesion was higher in inflamed aVEC sheared under multiaxial flow, which may be relevant to understanding the initial stages of CAVD.<\/jats:p>","DOI":"10.3390\/ijms221910605","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T10:22:42Z","timestamp":1632997362000},"page":"10605","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Interferons Are Pro-Inflammatory Cytokines in Sheared-Stressed Human Aortic Valve Endothelial Cells"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8831-1115","authenticated-orcid":false,"given":"Iv\u00e1n","family":"Parra-Izquierdo","sequence":"first","affiliation":[{"name":"Instituto de Biolog\u00eda y Gen\u00e9tica Molecular, Spanish National Research Council (CSIC), Universidad de Valladolid, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"S\u00e1nchez-Bayuela","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda y Gen\u00e9tica Molecular, Spanish National Research Council (CSIC), Universidad de Valladolid, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"ICICOR, Hospital Cl\u00ednico Universitario, 47005 Valladolid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda y Gen\u00e9tica Molecular, Spanish National Research Council (CSIC), Universidad de Valladolid, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"P\u00e9rez-Riesgo","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda y Gen\u00e9tica Molecular, Spanish National Research Council (CSIC), Universidad de Valladolid, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0764-0839","authenticated-orcid":false,"given":"J. Alberto","family":"San Rom\u00e1n","sequence":"additional","affiliation":[{"name":"ICICOR, Hospital Cl\u00ednico Universitario, 47005 Valladolid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6149-154X","authenticated-orcid":false,"given":"Mariano","family":"S\u00e1nchez Crespo","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda y Gen\u00e9tica Molecular, Spanish National Research Council (CSIC), Universidad de Valladolid, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdi","family":"Yacoub","sequence":"additional","affiliation":[{"name":"National Heart & Lung Institute, Imperial College London, London SW3 6LR, UK"},{"name":"Magdi Yacoub Institute, Harefield UB9 6JH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7002-1075","authenticated-orcid":false,"given":"Adrian H.","family":"Chester","sequence":"additional","affiliation":[{"name":"National Heart & Lung Institute, Imperial College London, London SW3 6LR, UK"},{"name":"Magdi Yacoub Institute, Harefield UB9 6JH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7205-4572","authenticated-orcid":false,"given":"Carmen","family":"Garc\u00eda-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda y Gen\u00e9tica Molecular, Spanish National Research Council (CSIC), Universidad de Valladolid, 47003 Valladolid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1161\/01.ATV.0000227513.13697.ac","article-title":"Pathogenesis of calcific aortic valve disease: A disease process comes of age (and a good deal more)","volume":"26","year":"2006","journal-title":"Arterioscler. 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