{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:50:45Z","timestamp":1793836245960,"version":"4.6.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T00:00:00Z","timestamp":1504224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Systemic lupus erythematosus (SLE) is a known risk factor for endothelial dysfunction. Murine and human lupus studies revealed a role for IFN-\u03b1 in vascular abnormalities associated with impaired blood vessel dilation. However, the impact of IFN-\u03b1 on mediators that induce vasodilation and modulate inflammation, including endothelial NO synthase (eNOS) and NO bioavailability, are unknown. The objectives of this study were to determine how IFN-\u03b1 promotes endothelial dysfunction in SLE, focusing on its regulation of eNOS and NO production in endothelial cells. We demonstrate that IFN-\u03b1 promotes an endothelial dysfunction signature in HUVECs that is characterized by transcription suppression and mRNA instability of eNOS complemented by upregulation of MCP1 and VCAM1. These changes are associated with IFN-inducible gene expression. IFN-\u03b1 impairs insulin-mediated NO production, and altered gene expression resulted from eNOS instability, possibly due to enhanced miR-155 expression. IFN-\u03b1 significantly impaired NO production in insulin-stimulated HUVECs. IFN-\u03b1 treatment also led to enhanced neutrophil adhesion. Our study introduces a novel pathway by which IFN-\u03b1 serves as a proatherogenic mediator through repression of eNOS-dependent pathways. This could promote the development of endothelial dysfunction and cardiovascular disease in SLE.<\/jats:p>","DOI":"10.4049\/jimmunol.1600108","type":"journal-article","created":{"date-parts":[[2017,8,4]],"date-time":"2017-08-04T20:40:24Z","timestamp":1501879224000},"page":"1979-1988","source":"Crossref","is-referenced-by-count":83,"title":["IFN-\u03b1 Negatively Regulates the Expression of Endothelial Nitric Oxide Synthase and Nitric Oxide Production: Implications for Systemic Lupus Erythematosus"],"prefix":"10.1093","volume":"199","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4026-4812","authenticated-orcid":false,"given":"Joy Jones","family":"Buie","sequence":"first","affiliation":[{"name":"Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina , Charleston, SC 29425"},{"name":"Department of Molecular and Cellular Biology and Pathobiology, Medical University of South Carolina , Charleston, SC 29425"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludivine L","family":"Renaud","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology and Pathobiology, Medical University of South Carolina , Charleston, SC 29425"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8840-4661","authenticated-orcid":false,"given":"Robin","family":"Muise-Helmericks","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina , Charleston, SC 29425"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5426-1359","authenticated-orcid":false,"given":"Jim C","family":"Oates","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina , Charleston, SC 29425"},{"name":"Medical Research Service, Ralph H. 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