{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T08:47:29Z","timestamp":1793090849989,"version":"4.5.0"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,3,17]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">The role of plasma and its components in the progression of aortic stenosis (AS) remains insufficiently investigated. This study aimed to assess whether plasma from patients with AS induces oxidative stress and contributes to valvular endothelial cells (VECs) dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">Human plasma samples were obtained from patients with severe AS (AS+, n=110), patients with cardiovascular risk factors without AS (n=30), and healthy individuals (n=15). Plasma levels of proinflammatory cytokines (IL [interleukin]\u20101\u03b2, IL\u20106, TNF [tumor necrosis factor]\u2010\u03b1, and factor Xa [FXa]) were measured. Porcine aortic VECs were then incubated with plasma (10%, 24 hours). Oxidative stress levels were assessed using dihydroethidium staining, NO formation with 4\u2010amino\u20105\u2010methylamino\u20102\u2032,7\u2032\u2010difluororescein diacetate, mRNA expression by quantitative reverse transcription\u2010polymerase chain reaction, and protein expression levels by Western blot analyses. Platelets and monocytes adhesion as well as thrombin generation were determined. Different pharmacological inhibitors were used to explore the underlying pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">Plasma from patients with AS+ exhibited elevated levels of IL\u20101\u03b2, IL\u20106, TNF\u2010\u03b1, and FXa activity. Incubation of VECs with AS+ plasma induced a pro\u2010oxidant response mediated by proinflammatory cytokines, the angiotensin system\u2010SGLT2 (sodium\u2010glucose transport protein 2) pathway, and FXa. AS+ plasma also triggered VEC dysfunction, inflammation, monocytes and platelets adhesion, and thrombin generation. These detrimental effects were mitigated by empagliflozin, losartan, neutralizing antibodies targeting proinflammatory cytokines, and dabigatran and rivaroxaban.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Patients with AS displayed subclinical systemic inflammation and increased FXa activity. These processes contributed to aortic VEC dysfunction, inflammation, monocytes and platelets adhesion, and thrombin generation upon exposure to AS+ plasma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.041701","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T12:27:10Z","timestamp":1764160030000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Detrimental Effect of Plasma From Patients With Severe Aortic Stenosis on Valvular Endothelial Cells: Role of Proinflammatory Cytokines and Factor Xa"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9279-4220","authenticated-orcid":false,"given":"Antonin","family":"Trimaille","sequence":"first","affiliation":[{"name":"Nouvel H\u00f4pital Civil, Strasbourg University Hospital","place":["Strasbourg, France"]},{"name":"Biomedicine Research Center of Strasbourg, University of 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