title: TMEM16F-Mediated Platelet Membrane Phospholipid Scrambling Is Critical for Hemostasis and Thrombosis but not Thromboinflammation in Mice-Brief Report.
abstract: It is known that both platelets and coagulation strongly influence infarct progression after ischemic stroke, but the mechanisms and their interplay are unknown. Our aim was to assess the contribution of the procoagulant platelet surface, and thus platelet-driven thrombin generation, to the progression of thromboinflammation in the ischemic brain.
  
  
  
  We present the characterization of a novel platelet and megakaryocyte-specific TMEM16F (anoctamin 6) knockout mouse. Reflecting Scott syndrome, platelets from the knockout mouse had a significant reduction in procoagulant characteristics that altered thrombin and fibrin generation kinetics. In addition, knockout mice showed significant defects in hemostasis and arterial thrombus formation. However, infarct volumes in a model of ischemic stroke were comparable with wild-type mice.
  
  
  
  Platelet TMEM16F activity contributes significantly to hemostasis and thrombosis but not cerebral thromboinflammation. These results highlight another key difference between the roles of platelets and coagulation in these processes.
authors.affiliation: From the Rudolf Virchow Center for Experimental Biomedicine (A.A.B., E.J.H., D.S., B.N.), Institute of Experimental Biomedicine (A.A.B., E.J.H., S.B., D.S., A.B., B.N.), and Department of Neurology (E.G., M.K.S., C.K.), University Hospital of Würzburg and University of Würzburg, Germany; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (F.S., J.W.M.H.); Department of Physiology, University of Regensburg, Germany (P.W., K.K.); and Clinic for Neurology, University of Duisburg-Essen Medical Facility, Essen, Germany (C.K.).
authors.forename: Ayesha A
authors.initials: AA
authors.lastname: Baig
authors.affiliation: From the Rudolf Virchow Center for Experimental Biomedicine (A.A.B., E.J.H., D.S., B.N.), Institute of Experimental Biomedicine (A.A.B., E.J.H., S.B., D.S., A.B., B.N.), and Department of Neurology (E.G., M.K.S., C.K.), University Hospital of Würzburg and University of Würzburg, Germany; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (F.S., J.W.M.H.); Department of Physiology, University of Regensburg, Germany (P.W., K.K.); and Clinic for Neurology, University of Duisburg-Essen Medical Facility, Essen, Germany (C.K.).
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Haining
authors.affiliation: From the Rudolf Virchow Center for Experimental Biomedicine (A.A.B., E.J.H., D.S., B.N.), Institute of Experimental Biomedicine (A.A.B., E.J.H., S.B., D.S., A.B., B.N.), and Department of Neurology (E.G., M.K.S., C.K.), University Hospital of Würzburg and University of Würzburg, Germany; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (F.S., J.W.M.H.); Department of Physiology, University of Regensburg, Germany (P.W., K.K.); and Clinic for Neurology, University of Duisburg-Essen Medical Facility, Essen, Germany (C.K.).
authors.forename: Eva
authors.initials: E
authors.lastname: Geuss
authors.affiliation: From the Rudolf Virchow Center for Experimental Biomedicine (A.A.B., E.J.H., D.S., B.N.), Institute of Experimental Biomedicine (A.A.B., E.J.H., S.B., D.S., A.B., B.N.), and Department of Neurology (E.G., M.K.S., C.K.), University Hospital of Würzburg and University of Würzburg, Germany; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (F.S., J.W.M.H.); Department of Physiology, University of Regensburg, Germany (P.W., K.K.); and Clinic for Neurology, University of Duisburg-Essen Medical Facility, Essen, Germany (C.K.).
authors.forename: Sarah
authors.initials: S
authors.lastname: Beck
authors.affiliation: From the Rudolf Virchow Center for Experimental Biomedicine (A.A.B., E.J.H., D.S., B.N.), Institute of Experimental Biomedicine (A.A.B., E.J.H., S.B., D.S., A.B., B.N.), and Department of Neurology (E.G., M.K.S., C.K.), University Hospital of Würzburg and University of Würzburg, Germany; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (F.S., J.W.M.H.); Department of Physiology, University of Regensburg, Germany (P.W., K.K.); and Clinic for Neurology, University of Duisburg-Essen Medical Facility, Essen, Germany (C.K.).
authors.forename: Frauke
authors.initials: F
authors.lastname: Swieringa
authors.affiliation: From the Rudolf Virchow Center for Experimental Biomedicine (A.A.B., E.J.H., D.S., B.N.), Institute of Experimental Biomedicine (A.A.B., E.J.H., S.B., D.S., A.B., B.N.), and Department of Neurology (E.G., M.K.S., C.K.), University Hospital of Würzburg and University of Würzburg, Germany; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (F.S., J.W.M.H.); Department of Physiology, University of Regensburg, Germany (P.W., K.K.); and Clinic for Neurology, University of Duisburg-Essen Medical Facility, Essen, Germany (C.K.).
authors.forename: Podchanart
authors.initials: P
authors.lastname: Wanitchakool
authors.affiliation: From the Rudolf Virchow Center for Experimental Biomedicine (A.A.B., E.J.H., D.S., B.N.), Institute of Experimental Biomedicine (A.A.B., E.J.H., S.B., D.S., A.B., B.N.), and Department of Neurology (E.G., M.K.S., C.K.), University Hospital of Würzburg and University of Würzburg, Germany; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (F.S., J.W.M.H.); Department of Physiology, University of Regensburg, Germany (P.W., K.K.); and Clinic for Neurology, University of Duisburg-Essen Medical Facility, Essen, Germany (C.K.).
authors.forename: Michael K
authors.initials: MK
authors.lastname: Schuhmann
authors.affiliation: From the Rudolf Virchow Center for Experimental Biomedicine (A.A.B., E.J.H., D.S., B.N.), Institute of Experimental Biomedicine (A.A.B., E.J.H., S.B., D.S., A.B., B.N.), and Department of Neurology (E.G., M.K.S., C.K.), University Hospital of Würzburg and University of Würzburg, Germany; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (F.S., J.W.M.H.); Department of Physiology, University of Regensburg, Germany (P.W., K.K.); and Clinic for Neurology, University of Duisburg-Essen Medical Facility, Essen, Germany (C.K.).
authors.forename: David
authors.initials: D
authors.lastname: Stegner
authors.affiliation: From the Rudolf Virchow Center for Experimental Biomedicine (A.A.B., E.J.H., D.S., B.N.), Institute of Experimental Biomedicine (A.A.B., E.J.H., S.B., D.S., A.B., B.N.), and Department of Neurology (E.G., M.K.S., C.K.), University Hospital of Würzburg and University of Würzburg, Germany; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (F.S., J.W.M.H.); Department of Physiology, University of Regensburg, Germany (P.W., K.K.); and Clinic for Neurology, University of Duisburg-Essen Medical Facility, Essen, Germany (C.K.).
authors.forename: Karl
authors.initials: K
authors.lastname: Kunzelmann
authors.affiliation: From the Rudolf Virchow Center for Experimental Biomedicine (A.A.B., E.J.H., D.S., B.N.), Institute of Experimental Biomedicine (A.A.B., E.J.H., S.B., D.S., A.B., B.N.), and Department of Neurology (E.G., M.K.S., C.K.), University Hospital of Würzburg and University of Würzburg, Germany; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (F.S., J.W.M.H.); Department of Physiology, University of Regensburg, Germany (P.W., K.K.); and Clinic for Neurology, University of Duisburg-Essen Medical Facility, Essen, Germany (C.K.).
authors.forename: Christoph
authors.initials: C
authors.lastname: Kleinschnitz
authors.affiliation: From the Rudolf Virchow Center for Experimental Biomedicine (A.A.B., E.J.H., D.S., B.N.), Institute of Experimental Biomedicine (A.A.B., E.J.H., S.B., D.S., A.B., B.N.), and Department of Neurology (E.G., M.K.S., C.K.), University Hospital of Würzburg and University of Würzburg, Germany; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (F.S., J.W.M.H.); Department of Physiology, University of Regensburg, Germany (P.W., K.K.); and Clinic for Neurology, University of Duisburg-Essen Medical Facility, Essen, Germany (C.K.).
authors.forename: Johan W M
authors.initials: JW
authors.lastname: Heemskerk
authors.affiliation: From the Rudolf Virchow Center for Experimental Biomedicine (A.A.B., E.J.H., D.S., B.N.), Institute of Experimental Biomedicine (A.A.B., E.J.H., S.B., D.S., A.B., B.N.), and Department of Neurology (E.G., M.K.S., C.K.), University Hospital of Würzburg and University of Würzburg, Germany; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (F.S., J.W.M.H.); Department of Physiology, University of Regensburg, Germany (P.W., K.K.); and Clinic for Neurology, University of Duisburg-Essen Medical Facility, Essen, Germany (C.K.).
authors.forename: Attila
authors.initials: A
authors.lastname: Braun
authors.affiliation: From the Rudolf Virchow Center for Experimental Biomedicine (A.A.B., E.J.H., D.S., B.N.), Institute of Experimental Biomedicine (A.A.B., E.J.H., S.B., D.S., A.B., B.N.), and Department of Neurology (E.G., M.K.S., C.K.), University Hospital of Würzburg and University of Würzburg, Germany; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (F.S., J.W.M.H.); Department of Physiology, University of Regensburg, Germany (P.W., K.K.); and Clinic for Neurology, University of Duisburg-Essen Medical Facility, Essen, Germany (C.K.). bernhard.nieswandt@virchow.uni-wuerzburg.de.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
mesh_terms: D000818:Animals; D000075368:Anoctamins; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism*; D002340:Carotid Artery Diseases / Q000097:blood* / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D004660:Encephalitis / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D005337:Fibrin / Q000378:metabolism; D006487:Hemostasis; D020244:Infarction, Middle Cerebral Artery / Q000097:blood* / Q000235:genetics / Q000473:pathology; D007700:Kinetics; D008533:Megakaryocytes / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010718:Phosphatidylserines / Q000097:blood*; D049294:Phospholipid Transfer Proteins / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D015539:Platelet Activation; D015398:Signal Transduction; D013917:Thrombin / Q000378:metabolism*; D013927:Thrombosis / Q000097:blood* / Q000235:genetics / Q000473:pathology
chemical_list: C576687:ANO6 protein, mouse; D000075368:Anoctamins; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; D005337:Fibrin; D013917:Thrombin
keywords: blood platelets; fibrin; stroke; thrombin; thrombosis