TY - JOUR A1 - Herzog, Christine A1 - Schmitz, Martina A1 - Levkau, Bodo A1 - Herrgott, Ilka A1 - Mersmann, Jan A1 - Larmann, Jan A1 - Johanning, Kai A1 - Winterhalter, Michael A1 - Chun, Jerold A1 - Müller, Frank Ulrich A1 - Echtermeyer, Frank A1 - Hildebrand, Reinhard A1 - Theilmeier, Gregor T1 - Intravenous sphingosylphosphorylcholine protects ischemic and postischemic myocardial tissue in a mouse model of myocardial ischemia/reperfusion injury T2 - Mediators of inflammation N2 - 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. Y1 - 2011 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/20673 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30-89145 SN - 1466-1861 SN - 0962-9351 N1 - Copyright © 2010 Christine Herzog et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. VL - 2010 IS - Art. 425191 SP - 1 EP - 7 PB - Hindawi Publishing Corp. CY - Sylvania, Ohio ER -