title: Microparticle-Induced Coagulation Relates to Coronary Artery Atherosclerosis in Severe Aortic Valve Stenosis.
abstract: BACKGROUND
  Circulating microparticles (MPs) derived from endothelial cells and blood cells bear procoagulant activity and promote thrombin generation. Thrombin exerts proinflammatory effects mediating the progression of atherosclerosis. Aortic valve stenosis may represent an atherosclerosis-like process involving both the aortic valve and the vascular system. The aim of this study was to investigate whether MP-induced thrombin generation is related to coronary atherosclerosis and aortic valve calcification.
  
  
  METHODS
  In a cross-sectional study of 55 patients with severe aortic valve stenosis, we assessed the coronary calcification score (CAC) as indicator of total coronary atherosclerosis burden, and aortic valve calcification (AVC) by computed tomography. Thrombin-antithrombin complex (TATc) levels were measured as a marker for thrombin formation. Circulating MPs were characterized by flow cytometry according to the expression of established surface antigens and by measuring MP-induced thrombin generation.
  
  
  RESULTS
  Patients with CAC score below the median were classified as patients with low CAC, patients with CAC Score above the median as high CAC. In patients with high CAC compared to patients with low CAC we detected higher levels of TATc, platelet-derived MPs (PMPs), endothelial-derived MPs (EMPs) and MP-induced thrombin generation. Increased level of PMPs and MP-induced thrombin generation were independent predictors for the severity of CAC. In contrast, AVC Score did not differ between patients with high and low CAC and did neither correlate with MPs levels nor with MP-induced thrombin generation.
  
  
  CONCLUSIONS
  In patients with severe aortic valve stenosis MP-induced thrombin generation was independently associated with the severity of CAC but not AVC indicating different pathomechanisms involved in coronary artery and aortic valve calcification.
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Düsseldorf, Düsseldorf, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Horn
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Düsseldorf, Düsseldorf, Germany.
authors.forename: Gülsüm
authors.initials: G
authors.lastname: Erkilet
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Düsseldorf, Düsseldorf, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Veulemans
authors.affiliation: Department of Diagnostic and Interventional Radiology, Medical Faculty, University Düsseldorf, Düsseldorf, Germany.
authors.forename: Patric
authors.initials: P
authors.lastname: Kröpil
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Leon
authors.initials: L
authors.lastname: Schurgers
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Düsseldorf, Düsseldorf, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Zeus
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Düsseldorf, Düsseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Düsseldorf, Düsseldorf, Germany.|Cardiovascular Research Institute Düsseldorf (CARID), Medical Faculty, University Düsseldorf, Düsseldorf, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Düsseldorf, Düsseldorf, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Westenfeld
mesh_terms: D000990:Antithrombin III; D001021:Aortic Valve / Q000473:pathology*; D001024:Aortic Valve Stenosis / Q000097:blood / Q000473:pathology*; D001777:Blood Coagulation; D002114:Calcinosis / Q000097:blood / Q000473:pathology*; D055252:Cell-Derived Microparticles / Q000473:pathology*; D003324:Coronary Artery Disease / Q000097:blood / Q000473:pathology*; D003331:Coronary Vessels / Q000473:pathology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D010447:Peptide Hydrolases / Q000097:blood; D013917:Thrombin / Q000032:analysis
chemical_list: C046193:antithrombin III-protease complex; D000990:Antithrombin III; D010447:Peptide Hydrolases; D013917:Thrombin