{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:38:48Z","timestamp":1790829528509,"version":"4.1.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"13","license":[{"start":{"date-parts":[[2023,7,30]],"date-time":"2023-07-30T00:00:00Z","timestamp":1690675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100012324","name":"University Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012324","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cardiac Research Network"},{"name":"Aortic VAlve"},{"name":"French Government"},{"name":"National Research Agency"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Inflammatory cytokines play a critical role in the progression of calcific aortic valve disease (CAVD), for which there is currently no pharmacological treatment. The aim of this study was to test the hypothesis that interleukin-8 (IL-8), known to be involved in arterial calcification, also promotes aortic valve calcification (AVC) and to evaluate whether pharmacologically blocking the IL-8 receptor, CXC motif chemokine receptor 2 (CXCR2), could be effective in preventing AVC progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>A cohort of 195 patients (median age 73, 74% men) diagnosed with aortic valve stenosis (severe in 16.9% of cases) were prospectively followed by CT for a median time of 2.6 years. A Cox proportional hazards regression analysis indicated that baseline IL-8 serum concentrations were associated with rapid progression of AVC, defined as an annualized change in the calcification score by CT \u2265 110 AU\/year, after adjustment for age, gender, bicuspid anatomy, and baseline disease severity. In vitro, exposure of primary human aortic valvular interstitial cells (hVICs) to 15 pg\/mL IL-8 induced a two-fold increase in inorganic phosphate (Pi)-induced calcification. IL-8 promoted NF\u03baB pathway activation, MMP-12 expression, and elastin degradation in hVICs exposed to Pi. These effects were prevented by SCH527123, an antagonist of CXCR2. The expression of CXCR2 was confirmed in hVICs and samples of aortic valves isolated from patients with CAVD, in which the receptor was mainly found in calcified areas, along with MMP-12 and a degraded form of elastin. Finally, in a rat model of chronic kidney disease-associated CAVD, SCH527123 treatment (1 mg\/kg\/day given orally for 11 weeks) limited the decrease in aortic cusp separation, the increase in maximal velocity of the transaortic jet, and the increase in aortic mean pressure gradient measured by echocardiography, effects that were associated with a reduction in hydroxyapatite deposition and MMP-12 expression in the aortic valves.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, these results highlight, for the first time, a significant role for IL-8 in the progression of CAVD by promoting calcification via a CXCR2- and MMP-12-dependent mechanism that leads to elastin degradation, and identify CXCR2 as a promising therapeutic target for the treatment of CAVD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvad117","type":"journal-article","created":{"date-parts":[[2023,7,30]],"date-time":"2023-07-30T13:06:48Z","timestamp":1690722408000},"page":"2355-2367","source":"Crossref","is-referenced-by-count":23,"title":["Aortic valve calcification is promoted by interleukin-8 and restricted through antagonizing CXC motif chemokine receptor 2"],"prefix":"10.1093","volume":"119","author":[{"given":"Kawthar","family":"Dhayni","sequence":"first","affiliation":[{"name":"MP3CV Laboratory , UPJV UR 7517, University of Picardie Jules Verne, Avenue Laennec, 80054 Amiens , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuthiline","family":"Chabry","sequence":"additional","affiliation":[{"name":"MP3CV Laboratory , UPJV UR 7517, University of Picardie Jules Verne, Avenue Laennec, 80054 Amiens , France"},{"name":"Department of Cardiac Surgery, CHU Amiens-Picardie , 1 Rd-Point du Pr. Christian Cabrol, 80054 Amiens , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"H\u00e9naut","sequence":"additional","affiliation":[{"name":"MP3CV Laboratory , UPJV UR 7517, University of Picardie Jules Verne, Avenue Laennec, 80054 Amiens , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carine","family":"Avondo","sequence":"additional","affiliation":[{"name":"MP3CV Laboratory , UPJV UR 7517, University of Picardie Jules Verne, Avenue Laennec, 80054 Amiens , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedric","family":"Boudot","sequence":"additional","affiliation":[{"name":"MP3CV Laboratory , UPJV UR 7517, University of Picardie Jules Verne, Avenue Laennec, 80054 Amiens , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakim","family":"Ouled-Haddou","sequence":"additional","affiliation":[{"name":"HEMATIM Laboratory , UPJV UR 4666, Universit\u00e9 de Picardie Jules Verne, Avenue Laennec, 80054 Amiens , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith","family":"Bigot-Corbel","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, CHU de Nantes , Bd Jacques-Monod, 44093 Saint-Herblain , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Touati","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, CHU Amiens-Picardie , 1 Rd-Point du Pr. Christian Cabrol, 80054 Amiens , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9120-9026","authenticated-orcid":false,"given":"Thierry","family":"Caus","sequence":"additional","affiliation":[{"name":"MP3CV Laboratory , UPJV UR 7517, University of Picardie Jules Verne, Avenue Laennec, 80054 Amiens , France"},{"name":"Department of Cardiac Surgery, CHU Amiens-Picardie , 1 Rd-Point du Pr. Christian Cabrol, 80054 Amiens , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hind","family":"Messaoudi","sequence":"additional","affiliation":[{"name":"EnVI Laboratory, INSERM UMR 1096, Rouen Normandy University , 22 Boulevard Gambetta, 76183 Rouen , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00e9my","family":"Bellien","sequence":"additional","affiliation":[{"name":"EnVI Laboratory, INSERM UMR 1096, Rouen Normandy University , 22 Boulevard Gambetta, 76183 Rouen , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7867-3668","authenticated-orcid":false,"given":"Christophe","family":"Tribouilloy","sequence":"additional","affiliation":[{"name":"MP3CV Laboratory , UPJV UR 7517, University of Picardie Jules Verne, Avenue Laennec, 80054 Amiens , France"},{"name":"Department of Cardiology, CHU Amiens-Picardie , 1 Rd-Point du Pr. Christian Cabrol, 80054 Amiens , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6278-5670","authenticated-orcid":false,"given":"David","family":"Messika-Zeitoun","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Ottawa Heart Institute , 40 Ruskin Street, Ottawa, Ontario , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazem","family":"Zibara","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Sciences, Lebanese University , Beirut , Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa\u00efd","family":"Kamel","sequence":"additional","affiliation":[{"name":"MP3CV Laboratory , UPJV UR 7517, University of Picardie Jules Verne, Avenue Laennec, 80054 Amiens , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0186-4797","authenticated-orcid":false,"given":"Youssef","family":"Bennis","sequence":"additional","affiliation":[{"name":"MP3CV Laboratory , UPJV UR 7517, University of Picardie Jules Verne, Avenue Laennec, 80054 Amiens , France"},{"name":"Department of Pharmacology, CHU Amiens-Picardie , 1 Rd-Point du Professeur Christian Cabrol, 80054 Amiens , France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,7,30]]},"reference":[{"key":"2023102421131228100_cvad117-B1","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/S0195-668X(03)00201-X","article-title":"A prospective survey of patients with valvular heart disease in Europe: the Euro Heart Survey on Valvular Heart Disease","volume":"24","author":"Iung","year":"2003","journal-title":"Eur Heart J"},{"key":"2023102421131228100_cvad117-B2","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.pcad.2014.02.006","article-title":"The global burden of aortic stenosis","volume":"56","author":"Thaden","year":"2014","journal-title":"Prog Cardiovasc Dis"},{"key":"2023102421131228100_cvad117-B3","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.ehj.2003.12.002","article-title":"Mild and moderate aortic stenosis. 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