{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T17:15:25Z","timestamp":1783790125896,"version":"3.55.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["204820\/Z\/16\/Z"],"award-info":[{"award-number":["204820\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["206369\/Z\/17\/Z"],"award-info":[{"award-number":["206369\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG\/13\/7\/30099"],"award-info":[{"award-number":["RG\/13\/7\/30099"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RE\/13\/5\/30177"],"award-info":[{"award-number":["RE\/13\/5\/30177"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["CH\/12\/4\/29762"],"award-info":[{"award-number":["CH\/12\/4\/29762"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001804","name":"Canada Research Chair","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["CRC-2021-00549"],"award-info":[{"award-number":["CRC-2021-00549"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008582","name":"McGill University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008582","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MICIU"},{"DOI":"10.13039\/501100011033","name":"AEI","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Interferon (IFN) alpha (IFN\u03b1) and lambda3 (IFN\u03bb3) constitute first-line responses of immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by increasing interferon-stimulated genes (ISGs). Prolonged IFN production may exacerbate inflammation, contributing to endotheliitis and vascular dysfunction in coronavirus disease 2019 (COVID-19). We investigated whether spike protein S1 (SP1) of SARS-CoV-2 via IFN influences inflammation in human vascular and lymphatic endothelial cells (ECs) and whether these processes contribute to vascular dysfunction in the context of hypertension. We focused on ISG15, a crucial immune protein that is also implicated in hypertension-associated vascular injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Exposure of microvascular ECs to SP1 of SARS-CoV-2-induced expression of ISGs: ISG15, MX1, and IFIT1. These effects were potentiated by IFNs and reduced by ADAM17 and STAT1 inhibition and genetic inhibition of IFN\u03b1 and beta receptor subunit 1 (IFNAR1). In microvascular ECs IFN\u03bb3 and IFN\u03b1 increased expression of ISGs, TMPRSS2, ADAM17, production of pro-inflammatory mediators (tumor necrosis factor [TNF]\u03b1, interleukin [IL]-6, plasminogen activator inhibitor [PAI]-1) and reduced phosphorylation of eNOS (Ser1177). In pulmonary, lymphatic, and aortic ECs, IFN\u03b1, but not IFN\u03bb3, increased expression of ISGs and IL-6. To explore the relevance in intact vessels, effects of IFNs were studied in isolated micro-vessels from wildtype (WT), hypertensive and ISG15\u2212\/\u2212 mice. IFN\u03b1, IFN\u03bb3, and SP1 reduced endothelium-dependent relaxation in WT vessels, whereas IFN\u03b1 increased contraction in vessels from hypertensive mice. Vascular dysfunction induced by IFN\u03b1, IFN\u03bb3 or spike protein was abrogated in vessels from ISG15\u2212\/\u2212 mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SP1 and IFNs synergically increase EC expression of ISGs through ADAM17. IFN\u03bb3 and IFN\u03b1 promote endothelial inflammation and vascular dysfunction through ISG15. These processes may play a role in the endotheliopathy and vascular damage associated with SP1 and might contribute to cardiovascular sequelae, including hypertension, of SARS-CoV-2 infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvag111","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T11:47:56Z","timestamp":1778845676000},"page":"1344-1358","source":"Crossref","is-referenced-by-count":0,"title":["Spike 1 protein of SARS-CoV-2 induces endothelial inflammation and vascular dysfunction through interferon ISG15-dependent mechanisms"],"prefix":"10.1093","volume":"122","author":[{"given":"Francisco J","family":"Rios","sequence":"first","affiliation":[{"name":"Department of Medicine, Research Institute of the McGill University Health Centre , 1001, boul D\u00e9carie, ES1.5066.6, Montreal, Qu\u00e9bec H4A 3J1 ,","place":["Canada"]},{"name":"School of Medicine, Pharmacy and Biomedical Sciences, University of Portsmouth , St Michael\u2019s building, White Swan Rd, Portsmouth PO1 2DT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto C","family":"Montezano","sequence":"additional","affiliation":[{"name":"Department of Medicine, Research Institute of the McGill University Health Centre , 1001, boul D\u00e9carie, ES1.5066.6, Montreal, Qu\u00e9bec H4A 3J1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia L","family":"Camargo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Research Institute of the McGill University Health Centre , 1001, boul D\u00e9carie, ES1.5066.6, Montreal, Qu\u00e9bec H4A 3J1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rheure A","family":"Lopes","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, British Heart Foundation (BHF), Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana B","family":"Garc\u00eda-Redondo","sequence":"additional","affiliation":[{"name":"Departmento de Fisiolog\u00eda, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid , Madrid ,","place":["Spain"]},{"name":"Department of Physiology, Universidad Aut\u00f3noma de Madrid, Instituto Investigaci\u00f3n Hospital Universitario La Paz (IdiPaz), Madrid ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elihu","family":"Aranday-Cortes","sequence":"additional","affiliation":[{"name":"Medical Research Council University of Glasgow Centre for Virus Research, Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8218-5579","authenticated-orcid":false,"given":"Ana M","family":"Briones","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares , Madrid ,","place":["Spain"]},{"name":"Departamento de Farmacolog\u00eda, Universidad Aut\u00f3noma de Madrid, Instituto de Investigaci\u00f3n Hospital La Paz , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2217-9948","authenticated-orcid":false,"given":"John","family":"McLauchlan","sequence":"additional","affiliation":[{"name":"Medical Research Council University of Glasgow Centre for Virus Research, Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0670-0887","authenticated-orcid":false,"given":"Rhian M","family":"Touyz","sequence":"additional","affiliation":[{"name":"Department of Medicine, Research Institute of the McGill University Health Centre , 1001, boul D\u00e9carie, ES1.5066.6, Montreal, Qu\u00e9bec H4A 3J1 ,","place":["Canada"]},{"name":"Departments of Medicine and Department of Family Medicine, McGill University , 1001, boul D\u00e9carie, ES1.5066.6, Montr\u00e9al, Qu\u00e9bec H4A 3J1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"2026071113022457600_cvag111-B1","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.chom.2020.05.008","article-title":"Type I and type III interferons - induction, signaling, evasion, and application to combat COVID-19","volume":"27","author":"Park","year":"2020","journal-title":"Cell Host Microbe"},{"key":"2026071113022457600_cvag111-B2","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1038\/s12276-021-00592-0","article-title":"Type I and III interferon responses in SARS-CoV-2 infection","volume":"53","author":"Kim","year":"2021","journal-title":"Exp Mol 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