title: Sphingosine 1-Phosphate Produced by Sphingosine Kinase 2 Intrinsically Controls Platelet Aggregation In Vitro and In Vivo.
abstract: BACKGROUND
  Platelets are known to play a crucial role in hemostasis. Sphingosine kinases (Sphk) 1 and 2 catalyze the conversion of sphingosine to the bioactive metabolite sphingosine 1-phosphate (S1P). Although platelets are able to secrete S1P on activation, little is known about a potential intrinsic effect of S1P on platelet function.
  
  
  OBJECTIVE
  To investigate the role of Sphk1- and Sphk2-derived S1P in the regulation of platelet function.
  
  
  RESULTS
  We found a 100-fold reduction in intracellular S1P levels in platelets derived from Sphk2(-/-) mutants compared with Sphk1(-/-) or wild-type mice, as analyzed by mass spectrometry. Sphk2(-/-) platelets also failed to secrete S1P on stimulation. Blood from Sphk2-deficient mice showed decreased aggregation after protease-activated receptor 4-peptide and adenosine diphosphate stimulation in vitro, as assessed by whole blood impedance aggregometry. We revealed that S1P controls platelet aggregation via the sphingosine 1-phosphate receptor 1 through modulation of protease-activated receptor 4-peptide and adenosine diphosphate-induced platelet activation. Finally, we show by intravital microscopy that defective platelet aggregation in Sphk2-deficient mice translates into reduced arterial thrombus stability in vivo.
  
  
  CONCLUSIONS
  We demonstrate that Sphk2 is the major Sphk isoform responsible for the generation of S1P in platelets and plays a pivotal intrinsic role in the control of platelet activation. Correspondingly, Sphk2-deficient mice are protected from arterial thrombosis after vascular injury, but have normal bleeding times. Targeting this pathway could therefore present a new therapeutic strategy to prevent thrombosis.
authors.affiliation: From the Medizinische Klinik und Poliklinik I, Klinikum der Universität München (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., V.B., J.B., I.S., M.L., K.R.L., S.M.), Department of Applied Physics, Center for NanoSciences (K.R.L.), and Walther-Straub-Institute of Pharmacology and Toxicology (M.M.y.S.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., J.B., I.S., M.L., M.M.y.S., S.M.); Heart Failure Institute, Research Center for Translational Medicine and Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China (L.Z.); Institute of Pharmacology, University of Bern, Bern, Switzerland (A.H.); Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany (J.M.P.); and Preclinical Safety (D.L., E.P.), and Autoimmunity, Transplantation and Inflammation (C.B., A.B., T.B.), Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Urtz
authors.affiliation: From the Medizinische Klinik und Poliklinik I, Klinikum der Universität München (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., V.B., J.B., I.S., M.L., K.R.L., S.M.), Department of Applied Physics, Center for NanoSciences (K.R.L.), and Walther-Straub-Institute of Pharmacology and Toxicology (M.M.y.S.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., J.B., I.S., M.L., M.M.y.S., S.M.); Heart Failure Institute, Research Center for Translational Medicine and Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China (L.Z.); Institute of Pharmacology, University of Bern, Bern, Switzerland (A.H.); Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany (J.M.P.); and Preclinical Safety (D.L., E.P.), and Autoimmunity, Transplantation and Inflammation (C.B., A.B., T.B.), Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Florian
authors.initials: F
authors.lastname: Gaertner
authors.affiliation: From the Medizinische Klinik und Poliklinik I, Klinikum der Universität München (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., V.B., J.B., I.S., M.L., K.R.L., S.M.), Department of Applied Physics, Center for NanoSciences (K.R.L.), and Walther-Straub-Institute of Pharmacology and Toxicology (M.M.y.S.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., J.B., I.S., M.L., M.M.y.S., S.M.); Heart Failure Institute, Research Center for Translational Medicine and Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China (L.Z.); Institute of Pharmacology, University of Bern, Bern, Switzerland (A.H.); Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany (J.M.P.); and Preclinical Safety (D.L., E.P.), and Autoimmunity, Transplantation and Inflammation (C.B., A.B., T.B.), Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: von Bruehl
authors.affiliation: From the Medizinische Klinik und Poliklinik I, Klinikum der Universität München (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., V.B., J.B., I.S., M.L., K.R.L., S.M.), Department of Applied Physics, Center for NanoSciences (K.R.L.), and Walther-Straub-Institute of Pharmacology and Toxicology (M.M.y.S.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., J.B., I.S., M.L., M.M.y.S., S.M.); Heart Failure Institute, Research Center for Translational Medicine and Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China (L.Z.); Institute of Pharmacology, University of Bern, Bern, Switzerland (A.H.); Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany (J.M.P.); and Preclinical Safety (D.L., E.P.), and Autoimmunity, Transplantation and Inflammation (C.B., A.B., T.B.), Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Sue
authors.initials: S
authors.lastname: Chandraratne
authors.affiliation: From the Medizinische Klinik und Poliklinik I, Klinikum der Universität München (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., V.B., J.B., I.S., M.L., K.R.L., S.M.), Department of Applied Physics, Center for NanoSciences (K.R.L.), and Walther-Straub-Institute of Pharmacology and Toxicology (M.M.y.S.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., J.B., I.S., M.L., M.M.y.S., S.M.); Heart Failure Institute, Research Center for Translational Medicine and Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China (L.Z.); Institute of Pharmacology, University of Bern, Bern, Switzerland (A.H.); Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany (J.M.P.); and Preclinical Safety (D.L., E.P.), and Autoimmunity, Transplantation and Inflammation (C.B., A.B., T.B.), Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Faridun
authors.initials: F
authors.lastname: Rahimi
authors.affiliation: From the Medizinische Klinik und Poliklinik I, Klinikum der Universität München (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., V.B., J.B., I.S., M.L., K.R.L., S.M.), Department of Applied Physics, Center for NanoSciences (K.R.L.), and Walther-Straub-Institute of Pharmacology and Toxicology (M.M.y.S.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., J.B., I.S., M.L., M.M.y.S., S.M.); Heart Failure Institute, Research Center for Translational Medicine and Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China (L.Z.); Institute of Pharmacology, University of Bern, Bern, Switzerland (A.H.); Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany (J.M.P.); and Preclinical Safety (D.L., E.P.), and Autoimmunity, Transplantation and Inflammation (C.B., A.B., T.B.), Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: From the Medizinische Klinik und Poliklinik I, Klinikum der Universität München (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., V.B., J.B., I.S., M.L., K.R.L., S.M.), Department of Applied Physics, Center for NanoSciences (K.R.L.), and Walther-Straub-Institute of Pharmacology and Toxicology (M.M.y.S.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., J.B., I.S., M.L., M.M.y.S., S.M.); Heart Failure Institute, Research Center for Translational Medicine and Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China (L.Z.); Institute of Pharmacology, University of Bern, Bern, Switzerland (A.H.); Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany (J.M.P.); and Preclinical Safety (D.L., E.P.), and Autoimmunity, Transplantation and Inflammation (C.B., A.B., T.B.), Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Mathias
authors.initials: M
authors.lastname: Orban
authors.affiliation: From the Medizinische Klinik und Poliklinik I, Klinikum der Universität München (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., V.B., J.B., I.S., M.L., K.R.L., S.M.), Department of Applied Physics, Center for NanoSciences (K.R.L.), and Walther-Straub-Institute of Pharmacology and Toxicology (M.M.y.S.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., J.B., I.S., M.L., M.M.y.S., S.M.); Heart Failure Institute, Research Center for Translational Medicine and Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China (L.Z.); Institute of Pharmacology, University of Bern, Bern, Switzerland (A.H.); Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany (J.M.P.); and Preclinical Safety (D.L., E.P.), and Autoimmunity, Transplantation and Inflammation (C.B., A.B., T.B.), Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Verena
authors.initials: V
authors.lastname: Barocke
authors.affiliation: From the Medizinische Klinik und Poliklinik I, Klinikum der Universität München (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., V.B., J.B., I.S., M.L., K.R.L., S.M.), Department of Applied Physics, Center for NanoSciences (K.R.L.), and Walther-Straub-Institute of Pharmacology and Toxicology (M.M.y.S.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., J.B., I.S., M.L., M.M.y.S., S.M.); Heart Failure Institute, Research Center for Translational Medicine and Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China (L.Z.); Institute of Pharmacology, University of Bern, Bern, Switzerland (A.H.); Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany (J.M.P.); and Preclinical Safety (D.L., E.P.), and Autoimmunity, Transplantation and Inflammation (C.B., A.B., T.B.), Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Beil
authors.affiliation: From the Medizinische Klinik und Poliklinik I, Klinikum der Universität München (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., V.B., J.B., I.S., M.L., K.R.L., S.M.), Department of Applied Physics, Center for NanoSciences (K.R.L.), and Walther-Straub-Institute of Pharmacology and Toxicology (M.M.y.S.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., J.B., I.S., M.L., M.M.y.S., S.M.); Heart Failure Institute, Research Center for Translational Medicine and Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China (L.Z.); Institute of Pharmacology, University of Bern, Bern, Switzerland (A.H.); Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany (J.M.P.); and Preclinical Safety (D.L., E.P.), and Autoimmunity, Transplantation and Inflammation (C.B., A.B., T.B.), Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Irene
authors.initials: I
authors.lastname: Schubert
authors.affiliation: From the Medizinische Klinik und Poliklinik I, Klinikum der Universität München (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., V.B., J.B., I.S., M.L., K.R.L., S.M.), Department of Applied Physics, Center for NanoSciences (K.R.L.), and Walther-Straub-Institute of Pharmacology and Toxicology (M.M.y.S.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., J.B., I.S., M.L., M.M.y.S., S.M.); Heart Failure Institute, Research Center for Translational Medicine and Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China (L.Z.); Institute of Pharmacology, University of Bern, Bern, Switzerland (A.H.); Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany (J.M.P.); and Preclinical Safety (D.L., E.P.), and Autoimmunity, Transplantation and Inflammation (C.B., A.B., T.B.), Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Lorenz
authors.affiliation: From the Medizinische Klinik und Poliklinik I, Klinikum der Universität München (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., V.B., J.B., I.S., M.L., K.R.L., S.M.), Department of Applied Physics, Center for NanoSciences (K.R.L.), and Walther-Straub-Institute of Pharmacology and Toxicology (M.M.y.S.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., J.B., I.S., M.L., M.M.y.S., S.M.); Heart Failure Institute, Research Center for Translational Medicine and Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China (L.Z.); Institute of Pharmacology, University of Bern, Bern, Switzerland (A.H.); Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany (J.M.P.); and Preclinical Safety (D.L., E.P.), and Autoimmunity, Transplantation and Inflammation (C.B., A.B., T.B.), Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Kyle R
authors.initials: KR
authors.lastname: Legate
authors.affiliation: From the Medizinische Klinik und Poliklinik I, Klinikum der Universität München (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., V.B., J.B., I.S., M.L., K.R.L., S.M.), Department of Applied Physics, Center for NanoSciences (K.R.L.), and Walther-Straub-Institute of Pharmacology and Toxicology (M.M.y.S.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., J.B., I.S., M.L., M.M.y.S., S.M.); Heart Failure Institute, Research Center for Translational Medicine and Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China (L.Z.); Institute of Pharmacology, University of Bern, Bern, Switzerland (A.H.); Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany (J.M.P.); and Preclinical Safety (D.L., E.P.), and Autoimmunity, Transplantation and Inflammation (C.B., A.B., T.B.), Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Huwiler
authors.affiliation: From the Medizinische Klinik und Poliklinik I, Klinikum der Universität München (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., V.B., J.B., I.S., M.L., K.R.L., S.M.), Department of Applied Physics, Center for NanoSciences (K.R.L.), and Walther-Straub-Institute of Pharmacology and Toxicology (M.M.y.S.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., J.B., I.S., M.L., M.M.y.S., S.M.); Heart Failure Institute, Research Center for Translational Medicine and Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China (L.Z.); Institute of Pharmacology, University of Bern, Bern, Switzerland (A.H.); Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany (J.M.P.); and Preclinical Safety (D.L., E.P.), and Autoimmunity, Transplantation and Inflammation (C.B., A.B., T.B.), Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Josef M
authors.initials: JM
authors.lastname: Pfeilschifter
authors.affiliation: From the Medizinische Klinik und Poliklinik I, Klinikum der Universität München (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., V.B., J.B., I.S., M.L., K.R.L., S.M.), Department of Applied Physics, Center for NanoSciences (K.R.L.), and Walther-Straub-Institute of Pharmacology and Toxicology (M.M.y.S.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., J.B., I.S., M.L., M.M.y.S., S.M.); Heart Failure Institute, Research Center for Translational Medicine and Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China (L.Z.); Institute of Pharmacology, University of Bern, Bern, Switzerland (A.H.); Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany (J.M.P.); and Preclinical Safety (D.L., E.P.), and Autoimmunity, Transplantation and Inflammation (C.B., A.B., T.B.), Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Beerli
authors.affiliation: From the Medizinische Klinik und Poliklinik I, Klinikum der Universität München (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., V.B., J.B., I.S., M.L., K.R.L., S.M.), Department of Applied Physics, Center for NanoSciences (K.R.L.), and Walther-Straub-Institute of Pharmacology and Toxicology (M.M.y.S.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., J.B., I.S., M.L., M.M.y.S., S.M.); Heart Failure Institute, Research Center for Translational Medicine and Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China (L.Z.); Institute of Pharmacology, University of Bern, Bern, Switzerland (A.H.); Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany (J.M.P.); and Preclinical Safety (D.L., E.P.), and Autoimmunity, Transplantation and Inflammation (C.B., A.B., T.B.), Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Ledieu
authors.affiliation: From the Medizinische Klinik und Poliklinik I, Klinikum der Universität München (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., V.B., J.B., I.S., M.L., K.R.L., S.M.), Department of Applied Physics, Center for NanoSciences (K.R.L.), and Walther-Straub-Institute of Pharmacology and Toxicology (M.M.y.S.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., J.B., I.S., M.L., M.M.y.S., S.M.); Heart Failure Institute, Research Center for Translational Medicine and Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China (L.Z.); Institute of Pharmacology, University of Bern, Bern, Switzerland (A.H.); Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany (J.M.P.); and Preclinical Safety (D.L., E.P.), and Autoimmunity, Transplantation and Inflammation (C.B., A.B., T.B.), Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Elke
authors.initials: E
authors.lastname: Persohn
authors.affiliation: From the Medizinische Klinik und Poliklinik I, Klinikum der Universität München (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., V.B., J.B., I.S., M.L., K.R.L., S.M.), Department of Applied Physics, Center for NanoSciences (K.R.L.), and Walther-Straub-Institute of Pharmacology and Toxicology (M.M.y.S.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., J.B., I.S., M.L., M.M.y.S., S.M.); Heart Failure Institute, Research Center for Translational Medicine and Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China (L.Z.); Institute of Pharmacology, University of Bern, Bern, Switzerland (A.H.); Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany (J.M.P.); and Preclinical Safety (D.L., E.P.), and Autoimmunity, Transplantation and Inflammation (C.B., A.B., T.B.), Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Billich
authors.affiliation: From the Medizinische Klinik und Poliklinik I, Klinikum der Universität München (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., V.B., J.B., I.S., M.L., K.R.L., S.M.), Department of Applied Physics, Center for NanoSciences (K.R.L.), and Walther-Straub-Institute of Pharmacology and Toxicology (M.M.y.S.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., J.B., I.S., M.L., M.M.y.S., S.M.); Heart Failure Institute, Research Center for Translational Medicine and Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China (L.Z.); Institute of Pharmacology, University of Bern, Bern, Switzerland (A.H.); Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany (J.M.P.); and Preclinical Safety (D.L., E.P.), and Autoimmunity, Transplantation and Inflammation (C.B., A.B., T.B.), Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Baumruker
authors.affiliation: From the Medizinische Klinik und Poliklinik I, Klinikum der Universität München (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., V.B., J.B., I.S., M.L., K.R.L., S.M.), Department of Applied Physics, Center for NanoSciences (K.R.L.), and Walther-Straub-Institute of Pharmacology and Toxicology (M.M.y.S.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., J.B., I.S., M.L., M.M.y.S., S.M.); Heart Failure Institute, Research Center for Translational Medicine and Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China (L.Z.); Institute of Pharmacology, University of Bern, Bern, Switzerland (A.H.); Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany (J.M.P.); and Preclinical Safety (D.L., E.P.), and Autoimmunity, Transplantation and Inflammation (C.B., A.B., T.B.), Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Mederos y Schnitzler
authors.affiliation: From the Medizinische Klinik und Poliklinik I, Klinikum der Universität München (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., V.B., J.B., I.S., M.L., K.R.L., S.M.), Department of Applied Physics, Center for NanoSciences (K.R.L.), and Walther-Straub-Institute of Pharmacology and Toxicology (M.M.y.S.), Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (N.U., F.G., M.-L.v.B., S.C., F.R., M.O., J.B., I.S., M.L., M.M.y.S., S.M.); Heart Failure Institute, Research Center for Translational Medicine and Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China (L.Z.); Institute of Pharmacology, University of Bern, Bern, Switzerland (A.H.); Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany (J.M.P.); and Preclinical Safety (D.L., E.P.), and Autoimmunity, Transplantation and Inflammation (C.B., A.B., T.B.), Novartis Institutes for BioMedical Research, Basel, Switzerland. steffen.massberg@med.uni-muenchen.de.
authors.forename: Steffen
authors.initials: S
authors.lastname: Massberg
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000097:blood; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000201:enzymology*; D020212:Carotid Artery Injuries / Q000097:blood / Q000201:enzymology; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000201:enzymology; D008246:Lysophospholipids / Q000097:blood*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D010979:Platelet Function Tests; D049349:Receptors, Lysosphingolipid / Q000097:blood; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood; D000081025:Sphingosine-1-Phosphate Receptors; D013927:Thrombosis / Q000097:blood / Q000201:enzymology / Q000517:prevention & control; D013928:Thromboxane A2 / Q000097:blood; D057772:Vascular System Injuries / Q000097:blood / Q000201:enzymology; D000099157:Sphingosine Kinase
chemical_list: D016718:Arachidonic Acid; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D049349:Receptors, Lysosphingolipid; D013110:Sphingosine; D000081025:Sphingosine-1-Phosphate Receptors; D013928:Thromboxane A2; D000099157:Sphingosine Kinase; C556330:S1pr1 protein, mouse; C060506:sphingosine 1-phosphate
keywords: blood platelets; platelet aggregation; sphingosine 1-phosphate; sphingosine kinase; thrombosis