Intravenous Sphingosylphosphorylcholine Protects Ischemic and Postischemic Myocardial Tissue in a Mouse Model of Myocardial Ischemia/Reperfusion Injury
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 mo...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2010-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2010/425191 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832564281077399552 |
|---|---|
| author | Christine Herzog Martina Schmitz Bodo Levkau Ilka Herrgott Jan Mersmann Jan Larmann Kai Johanning Michael Winterhalter Jerold Chun Frank Ulrich Müller Frank Echtermeyer Reinhard Hildebrand Gregor Theilmeier |
| author_facet | Christine Herzog Martina Schmitz Bodo Levkau Ilka Herrgott Jan Mersmann Jan Larmann Kai Johanning Michael Winterhalter Jerold Chun Frank Ulrich Müller Frank Echtermeyer Reinhard Hildebrand Gregor Theilmeier |
| author_sort | Christine Herzog |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9a7fbf5f493a40e6aeb456112e6149f7 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-9a7fbf5f493a40e6aeb456112e6149f72025-02-03T01:11:27ZengWileyMediators of Inflammation0962-93511466-18612010-01-01201010.1155/2010/425191425191Intravenous Sphingosylphosphorylcholine Protects Ischemic and Postischemic Myocardial Tissue in a Mouse Model of Myocardial Ischemia/Reperfusion InjuryChristine Herzog0Martina Schmitz1Bodo Levkau2Ilka Herrgott3Jan Mersmann4Jan Larmann5Kai Johanning6Michael Winterhalter7Jerold Chun8Frank Ulrich Müller9Frank Echtermeyer10Reinhard Hildebrand11Gregor Theilmeier12Department of Anaesthesiology and Intensive Care Medicine, Hannover Medical School, 30625 Hannover, GermanyInstitute for Anatomy and IZKF, Münster University Hospital, University of Münster, 48149 Münster, GermanyInstitute of Pathophysiology, Center of Internal Medicine, University Hospital of Essen, 45122 Essen, GermanyInstitute for Anatomy and IZKF, Münster University Hospital, University of Münster, 48149 Münster, GermanyInstitute for Anatomy and IZKF, Münster University Hospital, University of Münster, 48149 Münster, GermanyDepartment of Anaesthesiology and Intensive Care Medicine, Hannover Medical School, 30625 Hannover, GermanyDepartment of Anaesthesiology and Intensive Care Medicine, Hannover Medical School, 30625 Hannover, GermanyDepartment of Anaesthesiology and Intensive Care Medicine, Hannover Medical School, 30625 Hannover, GermanyDepartment of Molecular Biology, Helen L. Dorris Child and Adolescent Neuropsychiatric Disorder Institute, The Scripps Research Institute, La Jolla, CA 92037, USAInstitute of Pharmacology and Toxicology, University of Münster, 48149 Münster, GermanyDepartment of Anaesthesiology and Intensive Care Medicine, Hannover Medical School, 30625 Hannover, GermanyInstitute for Anatomy and IZKF, Münster University Hospital, University of Münster, 48149 Münster, GermanyDepartment of Anaesthesiology and Intensive Care Medicine, Hannover Medical School, 30625 Hannover, GermanyHDL, 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.http://dx.doi.org/10.1155/2010/425191 |
| spellingShingle | Christine Herzog Martina Schmitz Bodo Levkau Ilka Herrgott Jan Mersmann Jan Larmann Kai Johanning Michael Winterhalter Jerold Chun Frank Ulrich Müller Frank Echtermeyer Reinhard Hildebrand Gregor Theilmeier Intravenous Sphingosylphosphorylcholine Protects Ischemic and Postischemic Myocardial Tissue in a Mouse Model of Myocardial Ischemia/Reperfusion Injury Mediators of Inflammation |
| title | Intravenous Sphingosylphosphorylcholine Protects Ischemic and Postischemic Myocardial Tissue in a Mouse Model of Myocardial Ischemia/Reperfusion Injury |
| title_full | Intravenous Sphingosylphosphorylcholine Protects Ischemic and Postischemic Myocardial Tissue in a Mouse Model of Myocardial Ischemia/Reperfusion Injury |
| title_fullStr | Intravenous Sphingosylphosphorylcholine Protects Ischemic and Postischemic Myocardial Tissue in a Mouse Model of Myocardial Ischemia/Reperfusion Injury |
| title_full_unstemmed | Intravenous Sphingosylphosphorylcholine Protects Ischemic and Postischemic Myocardial Tissue in a Mouse Model of Myocardial Ischemia/Reperfusion Injury |
| title_short | Intravenous Sphingosylphosphorylcholine Protects Ischemic and Postischemic Myocardial Tissue in a Mouse Model of Myocardial Ischemia/Reperfusion Injury |
| title_sort | intravenous sphingosylphosphorylcholine protects ischemic and postischemic myocardial tissue in a mouse model of myocardial ischemia reperfusion injury |
| url | http://dx.doi.org/10.1155/2010/425191 |
| work_keys_str_mv | AT christineherzog intravenoussphingosylphosphorylcholineprotectsischemicandpostischemicmyocardialtissueinamousemodelofmyocardialischemiareperfusioninjury AT martinaschmitz intravenoussphingosylphosphorylcholineprotectsischemicandpostischemicmyocardialtissueinamousemodelofmyocardialischemiareperfusioninjury AT bodolevkau intravenoussphingosylphosphorylcholineprotectsischemicandpostischemicmyocardialtissueinamousemodelofmyocardialischemiareperfusioninjury AT ilkaherrgott intravenoussphingosylphosphorylcholineprotectsischemicandpostischemicmyocardialtissueinamousemodelofmyocardialischemiareperfusioninjury AT janmersmann intravenoussphingosylphosphorylcholineprotectsischemicandpostischemicmyocardialtissueinamousemodelofmyocardialischemiareperfusioninjury AT janlarmann intravenoussphingosylphosphorylcholineprotectsischemicandpostischemicmyocardialtissueinamousemodelofmyocardialischemiareperfusioninjury AT kaijohanning intravenoussphingosylphosphorylcholineprotectsischemicandpostischemicmyocardialtissueinamousemodelofmyocardialischemiareperfusioninjury AT michaelwinterhalter intravenoussphingosylphosphorylcholineprotectsischemicandpostischemicmyocardialtissueinamousemodelofmyocardialischemiareperfusioninjury AT jeroldchun intravenoussphingosylphosphorylcholineprotectsischemicandpostischemicmyocardialtissueinamousemodelofmyocardialischemiareperfusioninjury AT frankulrichmuller intravenoussphingosylphosphorylcholineprotectsischemicandpostischemicmyocardialtissueinamousemodelofmyocardialischemiareperfusioninjury AT frankechtermeyer intravenoussphingosylphosphorylcholineprotectsischemicandpostischemicmyocardialtissueinamousemodelofmyocardialischemiareperfusioninjury AT reinhardhildebrand intravenoussphingosylphosphorylcholineprotectsischemicandpostischemicmyocardialtissueinamousemodelofmyocardialischemiareperfusioninjury AT gregortheilmeier intravenoussphingosylphosphorylcholineprotectsischemicandpostischemicmyocardialtissueinamousemodelofmyocardialischemiareperfusioninjury |