%0 Journal Article
%A Mueller, Karin Anne Lydia
%A Langnau, Carolin
%A Harm, Tobias
%A Sigle, Manuel
%A Mott, Kristina
%A Droppa, Michal
%A Borst, Oliver
%A Rohlfing, Anne-Katrin
%A Gekeler, Sarah
%A Günter, Manina
%A Goebel, Nora
%A Franke, Ulrich F W
%A Radwan, Medhat
%A Schlensak, Christian
%A Janning, Henrik
%A Scheuermann, Sophia
%A Seitz, Christian M
%A Rath, Dominik
%A Kreisselmeier, Klaus-Peter
%A Castor, Tatsiana
%A Mueller, Iris Irmgard
%A Schulze, Harald
%A Autenrieth, Stella
%A Gawaz, Meinrad Paul
%T Macrophage Migration Inhibitory Factor Promotes Thromboinflammation and Predicts Fast Progression of Aortic Stenosis.
%J Arteriosclerosis, thrombosis, and vascular biology
%V 44
%N 9
%@ 0276-5047
%C Stanford, Calif.
%I HighWire
%M DKFZ-2024-01453
%P 2118-2135
%D 2024
%Z #LA:D431# / 2024 Sep;44(9):2118-2135
%X 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.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.The patients were classified as fast-progressive AS by the median ∆Vmax 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 [142.3-504] versus 717.5 [360.5-1234]; P<0.001) with less calcification (calcification area, mm2: 33.74 [27.82-41.86] versus 20.54 [13.52-33.41]; P<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±SEM; 6877±379.1 versus 9959±749.1; P<0.001), increased platelet activation, and decreased intracellular MIF expression indicating enhanced MIF release upon platelet activation (CD62P, 
%K aortic valve stenosis (Other)
%K biomarkers (Other)
%K blood platelets (Other)
%K chemokines (Other)
%K inflammation (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:38989580
%R 10.1161/ATVBAHA.124.321000
%U https://inrepo02.dkfz.de/record/291568