PMID- 27010400 OWN - NLM STAT- MEDLINE DCOM- 20160811 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 11 IP - 3 DP - 2016 TI - Microparticle-Induced Coagulation Relates to Coronary Artery Atherosclerosis in Severe Aortic Valve Stenosis. PG - e0151499 LID - 10.1371/journal.pone.0151499 [doi] LID - e0151499 AB - 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. CONCLUSION: 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. FAU - Horn, Patrick AU - Horn P AD - Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Dusseldorf, Dusseldorf, Germany. FAU - Erkilet, Gulsum AU - Erkilet G AD - Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Dusseldorf, Dusseldorf, Germany. FAU - Veulemans, Verena AU - Veulemans V AD - Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Dusseldorf, Dusseldorf, Germany. FAU - Kropil, Patric AU - Kropil P AD - Department of Diagnostic and Interventional Radiology, Medical Faculty, University Dusseldorf, Dusseldorf, Germany. FAU - Schurgers, Leon AU - Schurgers L AD - Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands. FAU - Zeus, Tobias AU - Zeus T AD - Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Dusseldorf, Dusseldorf, Germany. FAU - Heiss, Christian AU - Heiss C AD - Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Dusseldorf, Dusseldorf, Germany. FAU - Kelm, Malte AU - Kelm M AD - Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Dusseldorf, Dusseldorf, Germany. AD - Cardiovascular Research Institute Dusseldorf (CARID), Medical Faculty, University Dusseldorf, Dusseldorf, Germany. FAU - Westenfeld, Ralf AU - Westenfeld R AD - Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Dusseldorf, Dusseldorf, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160324 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (antithrombin III-protease complex) RN - 9000-94-6 (Antithrombin III) RN - EC 3.4.- (Peptide Hydrolases) RN - EC 3.4.21.5 (Thrombin) RN - Aortic Valve, Calcification of SB - IM MH - Antithrombin III MH - Aortic Valve/*pathology MH - Aortic Valve Stenosis/blood/*pathology MH - Blood Coagulation MH - Calcinosis/blood/*pathology MH - Cell-Derived Microparticles/*pathology MH - Coronary Artery Disease/blood/*pathology MH - Coronary Vessels/*pathology MH - Cross-Sectional Studies MH - Female MH - Humans MH - Male MH - Peptide Hydrolases/blood MH - Thrombin/analysis PMC - PMC4807100 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2016/03/25 06:00 MHDA- 2016/08/12 06:00 PMCR- 2016/03/24 CRDT- 2016/03/25 06:00 PHST- 2015/11/25 00:00 [received] PHST- 2016/02/29 00:00 [accepted] PHST- 2016/03/25 06:00 [entrez] PHST- 2016/03/25 06:00 [pubmed] PHST- 2016/08/12 06:00 [medline] PHST- 2016/03/24 00:00 [pmc-release] AID - PONE-D-15-51352 [pii] AID - 10.1371/journal.pone.0151499 [doi] PST - epublish SO - PLoS One. 2016 Mar 24;11(3):e0151499. doi: 10.1371/journal.pone.0151499. eCollection 2016.