title: Intravenous sphingosylphosphorylcholine protects ischemic and postischemic myocardial tissue in a mouse model of myocardial ischemia/reperfusion injury.
abstract: HDL, through sphingosine-1-phosphate (S1P), exerts direct cardioprotective effects on ischemic myocardium. It remains unclear whether other HDL-associated sphingophospholipids have similar effects. We therefore examined if HDL-associated sphingosylphosphorylcholine (SPC) reduces infarct size in a mouse model of transient myocardial ischemia/reperfusion. Intravenously administered SPC dose-dependently reduced infarct size after 30 minutes of myocardial ischemia and 24 hours reperfusion compared to controls. Infarct size was also reduced by postischemic, therapeutical administration of SPC. Immunohistochemistry revealed reduced polymorphonuclear neutrophil recruitment to the infarcted area after SPC treatment, and apoptosis was attenuated as measured by TUNEL. In vitro, SPC inhibited leukocyte adhesion to TNFα-activated endothelial cells and protected rat neonatal cardiomyocytes from apoptosis. S1P₃ was identified as the lysophospholipid receptor mediating the cardioprotection by SPC, since its effect was completely absent in S1P₃-deficient mice. We conclude that HDL-associated SPC directly protects against myocardial reperfusion injury in vivo via the S1P₃ receptor.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Herzog
authors.forename: Martina
authors.initials: M
authors.lastname: Schmitz
authors.forename: Bodo
authors.initials: B
authors.lastname: Levkau
authors.forename: Ilka
authors.initials: I
authors.lastname: Herrgott
authors.forename: Jan
authors.initials: J
authors.lastname: Mersmann
authors.forename: Jan
authors.initials: J
authors.lastname: Larmann
authors.forename: Kai
authors.initials: K
authors.lastname: Johanning
authors.forename: Michael
authors.initials: M
authors.lastname: Winterhalter
authors.forename: Jerold
authors.initials: J
authors.lastname: Chun
authors.forename: Frank Ulrich
authors.initials: FU
authors.lastname: Müller
authors.forename: Frank
authors.initials: F
authors.lastname: Echtermeyer
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hildebrand
authors.forename: Gregor
authors.initials: G
authors.lastname: Theilmeier
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D002316:Cardiotonic Agents; D008075:Lipoproteins, HDL; D008246:Lysophospholipids; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; C060506:sphingosine 1-phosphate; D013110:Sphingosine