{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T02:40:27Z","timestamp":1792636827420,"version":"4.5.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","license":[{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Aortic stenosis (AS) is driven by progressive inflammatory and fibrocalcific processes regulated by circulating inflammatory and valve resident endothelial and interstitial cells. The impact of platelets, platelet-derived mediators, and platelet-monocyte interactions on the acceleration of local valvular inflammation and mineralization is presently unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>We prospectively enrolled 475 consecutive patients with severe symptomatic AS undergoing aortic valve replacement. Clinical workup included repetitive echocardiography, analysis of platelets, monocytes, chemokine profiling, aortic valve tissue samples for immunohistochemistry, and gene expression analysis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              The patients were classified as fast-progressive AS by the median \u2206Vmax of 0.45 m\/s per year determined by echocardiography. Immunohistological aortic valve analysis revealed enhanced cellularity in fast-progressive AS (slow- versus fast-progressive AS; median [interquartile range], 247 [142.3\u2013504] versus 717.5 [360.5\u20131234];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.001) with less calcification (calcification area, mm\n              <jats:sup>2<\/jats:sup>\n              : 33.74 [27.82\u201341.86] versus 20.54 [13.52\u201333.41];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.001). MIF (macrophage migration inhibitory factor)-associated gene expression was significantly enhanced in fast-progressive AS accompanied by significantly elevated MIF plasma levels (mean\u00b1SEM; 6877\u00b1379.1 versus 9959\u00b1749.1;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.001), increased platelet activation, and decreased intracellular MIF expression indicating enhanced MIF release upon platelet activation (CD62P, %: median [interquartile range], 16.8 [11.58\u201323.8] versus 20.55 [12.48\u201332.28],\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.005; MIF, %: 4.85 [1.48\u20139.75] versus 2.3 [0.78\u20135.9],\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.001). Regression analysis confirmed that MIF-associated biomarkers are strongly associated with an accelerated course of AS.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Our findings suggest a key role for platelet-derived MIF and its interplay with circulating and valve resident monocytes\/macrophages in local and systemic thromboinflammation during accelerated AS. MIF-based biomarkers predict an accelerated course of AS and represent a novel pharmacological target to attenuate progression of AS.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.124.321000","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T09:01:02Z","timestamp":1720688462000},"page":"2118-2135","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Macrophage Migration Inhibitory Factor Promotes Thromboinflammation and Predicts Fast Progression of Aortic Stenosis"],"prefix":"10.1161","volume":"44","author":[{"given":"Karin Anne Lydia","family":"Mueller","sequence":"first","affiliation":[{"name":"Department of Cardiology and Angiology (K.A.L.M., C.L., T.H., M.S., M.D., O.B., A.-K.R., S.G., H.J., D.R., K.-P.K., T.C., I.I.M., M.P.G.), University Hospital Tuebingen, Eberhard Karls University Tuebingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin","family":"Langnau","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology (K.A.L.M., C.L., T.H., M.S., M.D., O.B., A.-K.R., S.G., H.J., D.R., K.-P.K., T.C., I.I.M., M.P.G.), University Hospital Tuebingen, Eberhard Karls University Tuebingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6121-2694","authenticated-orcid":true,"given":"Tobias","family":"Harm","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology (K.A.L.M., C.L., T.H., M.S., M.D., O.B., A.-K.R., S.G., H.J., D.R., K.-P.K., T.C., I.I.M., M.P.G.), University Hospital Tuebingen, Eberhard Karls University Tuebingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8954-4810","authenticated-orcid":true,"given":"Manuel","family":"Sigle","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology (K.A.L.M., C.L., T.H., M.S., M.D., O.B., A.-K.R., S.G., H.J., D.R., K.-P.K., T.C., I.I.M., M.P.G.), University Hospital Tuebingen, Eberhard Karls University Tuebingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3223-6857","authenticated-orcid":true,"given":"Kristina","family":"Mott","sequence":"additional","affiliation":[{"name":"Institute for Experimental Biomedicine, Chair I University Hospital W\u00fcrzburg, Germany (K.M., H.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5807-7615","authenticated-orcid":true,"given":"Michal","family":"Droppa","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology (K.A.L.M., C.L., T.H., M.S., M.D., O.B., A.-K.R., S.G., H.J., D.R., K.-P.K., T.C., I.I.M., M.P.G.), University Hospital Tuebingen, Eberhard Karls University Tuebingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4002-4085","authenticated-orcid":true,"given":"Oliver","family":"Borst","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology (K.A.L.M., C.L., T.H., M.S., M.D., O.B., A.-K.R., S.G., H.J., D.R., K.-P.K., T.C., I.I.M., M.P.G.), University Hospital Tuebingen, Eberhard Karls University Tuebingen, Germany."},{"name":"DFG Heisenberg Group Thrombocardiology (O.B.), University of T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5469-3648","authenticated-orcid":true,"given":"Anne-Katrin","family":"Rohlfing","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology 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