High-density lipoproteins and their constituent, sphingosine-1-phosphate, directly protect the heart against ischemia/reperfusion injury in vivo via the S1P3 lysophospholipid receptor
All treatments of acute myocardial infarction are aimed at rapid revascularization of the occluded vessel; however, no clinical strategies are currently available to protect the heart from ischemia/reperfusion injury after restitution of blood flow. We hypothesized that some of the cholesterol trans...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2006-09, Vol.114 (13), p.1403-1409 |
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| creator | THEILMEIER, Gregor SCHMIDT, Christoph SCHOBER, Otmar HILDEBRAND, Reinhard SCHULZ, Rainer HEUSCH, Gerd HAUDE, Michael VON WNUCK LIPINSKI, Karin HERZOG, Christine SCHMITZ, Martina ERBEL, Raimund CHUN, Jerold HERRMANN, Jörg LEVKAU, Bodo KEUL, Petra SCHÄFERS, Michael HERRGOTT, Ilka MERSMANN, Jan LARMANN, Jan HERMANN, Sven STYPMANN, Jörg |
| description | All treatments of acute myocardial infarction are aimed at rapid revascularization of the occluded vessel; however, no clinical strategies are currently available to protect the heart from ischemia/reperfusion injury after restitution of blood flow. We hypothesized that some of the cholesterol transport-independent biological properties of high-density lipoprotein (HDL) implied in atheroprotection may also be beneficial in settings of acute myocardial reperfusion injury.
In an in vivo mouse model of myocardial ischemia/reperfusion, we observed that HDL and its sphingolipid component, sphingosine-1-phosphate (S1P), dramatically attenuated infarction size by approximately 20% and 40%, respectively. The underlying mechanism was an inhibition of inflammatory neutrophil recruitment and cardiomyocyte apoptosis in the infarcted area. In vitro, HDL and S1P potently suppressed leukocyte adhesion to activated endothelium under flow and protected rat neonatal cardiomyocytes against apoptosis. In vivo, HDL- and S1P-mediated cardioprotection was dependent on nitric oxide (NO) and the S1P3 lysophospholipid receptor, because it was abolished by pharmacological NO synthase inhibition and was completely absent in S1P3-deficient mice.
Our data demonstrate that HDL and its constituent, S1P, acutely protect the heart against ischemia/reperfusion injury in vivo via an S1P3-mediated and NO-dependent pathway. A rapid therapeutic elevation of S1P-containing HDL plasma levels may be beneficial in patients at high risk of acute myocardial ischemia. |
| doi_str_mv | 10.1161/CIRCULATIONAHA.105.607135 |
| format | Article |
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In an in vivo mouse model of myocardial ischemia/reperfusion, we observed that HDL and its sphingolipid component, sphingosine-1-phosphate (S1P), dramatically attenuated infarction size by approximately 20% and 40%, respectively. The underlying mechanism was an inhibition of inflammatory neutrophil recruitment and cardiomyocyte apoptosis in the infarcted area. In vitro, HDL and S1P potently suppressed leukocyte adhesion to activated endothelium under flow and protected rat neonatal cardiomyocytes against apoptosis. In vivo, HDL- and S1P-mediated cardioprotection was dependent on nitric oxide (NO) and the S1P3 lysophospholipid receptor, because it was abolished by pharmacological NO synthase inhibition and was completely absent in S1P3-deficient mice.
Our data demonstrate that HDL and its constituent, S1P, acutely protect the heart against ischemia/reperfusion injury in vivo via an S1P3-mediated and NO-dependent pathway. A rapid therapeutic elevation of S1P-containing HDL plasma levels may be beneficial in patients at high risk of acute myocardial ischemia.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/CIRCULATIONAHA.105.607135</identifier><identifier>PMID: 16982942</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Animals ; Antihypertensive agents ; Apoptosis - drug effects ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cardiotonic Agents - pharmacology ; Cardiotonic Agents - therapeutic use ; Cardiovascular system ; Cell Adhesion - drug effects ; Cells, Cultured - drug effects ; Chemotaxis, Leukocyte - drug effects ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Endothelial Cells - drug effects ; Endothelial Cells - physiology ; Female ; Humans ; Lipoproteins, HDL - pharmacology ; Lipoproteins, HDL - physiology ; Lipoproteins, HDL - therapeutic use ; Lipoproteins, LDL - pharmacology ; Lysophospholipids - pharmacology ; Lysophospholipids - physiology ; Lysophospholipids - therapeutic use ; Macrophages - physiology ; Male ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myocardial Ischemia - drug therapy ; Myocardial Reperfusion Injury - prevention & control ; Myocytes, Cardiac - drug effects ; Myocytes, Cardiac - pathology ; NG-Nitroarginine Methyl Ester - pharmacology ; Nitric Oxide - physiology ; Nitric Oxide Synthase - antagonists & inhibitors ; Pharmacology. Drug treatments ; Receptors, Lysosphingolipid - deficiency ; Receptors, Lysosphingolipid - drug effects ; Receptors, Lysosphingolipid - genetics ; Receptors, Lysosphingolipid - physiology ; Sphingosine - analogs & derivatives ; Sphingosine - pharmacology ; Sphingosine - physiology ; Sphingosine - therapeutic use ; Tumor Necrosis Factor-alpha - pharmacology ; Vasodilator agents. Cerebral vasodilators</subject><ispartof>Circulation (New York, N.Y.), 2006-09, Vol.114 (13), p.1403-1409</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18164814$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16982942$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>THEILMEIER, Gregor</creatorcontrib><creatorcontrib>SCHMIDT, Christoph</creatorcontrib><creatorcontrib>SCHOBER, Otmar</creatorcontrib><creatorcontrib>HILDEBRAND, Reinhard</creatorcontrib><creatorcontrib>SCHULZ, Rainer</creatorcontrib><creatorcontrib>HEUSCH, Gerd</creatorcontrib><creatorcontrib>HAUDE, Michael</creatorcontrib><creatorcontrib>VON WNUCK LIPINSKI, Karin</creatorcontrib><creatorcontrib>HERZOG, Christine</creatorcontrib><creatorcontrib>SCHMITZ, Martina</creatorcontrib><creatorcontrib>ERBEL, Raimund</creatorcontrib><creatorcontrib>CHUN, Jerold</creatorcontrib><creatorcontrib>HERRMANN, Jörg</creatorcontrib><creatorcontrib>LEVKAU, Bodo</creatorcontrib><creatorcontrib>KEUL, Petra</creatorcontrib><creatorcontrib>SCHÄFERS, Michael</creatorcontrib><creatorcontrib>HERRGOTT, Ilka</creatorcontrib><creatorcontrib>MERSMANN, Jan</creatorcontrib><creatorcontrib>LARMANN, Jan</creatorcontrib><creatorcontrib>HERMANN, Sven</creatorcontrib><creatorcontrib>STYPMANN, Jörg</creatorcontrib><title>High-density lipoproteins and their constituent, sphingosine-1-phosphate, directly protect the heart against ischemia/reperfusion injury in vivo via the S1P3 lysophospholipid receptor</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>All treatments of acute myocardial infarction are aimed at rapid revascularization of the occluded vessel; however, no clinical strategies are currently available to protect the heart from ischemia/reperfusion injury after restitution of blood flow. We hypothesized that some of the cholesterol transport-independent biological properties of high-density lipoprotein (HDL) implied in atheroprotection may also be beneficial in settings of acute myocardial reperfusion injury.
In an in vivo mouse model of myocardial ischemia/reperfusion, we observed that HDL and its sphingolipid component, sphingosine-1-phosphate (S1P), dramatically attenuated infarction size by approximately 20% and 40%, respectively. The underlying mechanism was an inhibition of inflammatory neutrophil recruitment and cardiomyocyte apoptosis in the infarcted area. In vitro, HDL and S1P potently suppressed leukocyte adhesion to activated endothelium under flow and protected rat neonatal cardiomyocytes against apoptosis. In vivo, HDL- and S1P-mediated cardioprotection was dependent on nitric oxide (NO) and the S1P3 lysophospholipid receptor, because it was abolished by pharmacological NO synthase inhibition and was completely absent in S1P3-deficient mice.
Our data demonstrate that HDL and its constituent, S1P, acutely protect the heart against ischemia/reperfusion injury in vivo via an S1P3-mediated and NO-dependent pathway. A rapid therapeutic elevation of S1P-containing HDL plasma levels may be beneficial in patients at high risk of acute myocardial ischemia.</description><subject>Animals</subject><subject>Antihypertensive agents</subject><subject>Apoptosis - drug effects</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Cardiotonic Agents - pharmacology</subject><subject>Cardiotonic Agents - therapeutic use</subject><subject>Cardiovascular system</subject><subject>Cell Adhesion - drug effects</subject><subject>Cells, Cultured - drug effects</subject><subject>Chemotaxis, Leukocyte - drug effects</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Endothelial Cells - drug effects</subject><subject>Endothelial Cells - physiology</subject><subject>Female</subject><subject>Humans</subject><subject>Lipoproteins, HDL - pharmacology</subject><subject>Lipoproteins, HDL - physiology</subject><subject>Lipoproteins, HDL - therapeutic use</subject><subject>Lipoproteins, LDL - pharmacology</subject><subject>Lysophospholipids - pharmacology</subject><subject>Lysophospholipids - physiology</subject><subject>Lysophospholipids - therapeutic use</subject><subject>Macrophages - physiology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Myocardial Ischemia - drug therapy</subject><subject>Myocardial Reperfusion Injury - prevention & control</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Myocytes, Cardiac - pathology</subject><subject>NG-Nitroarginine Methyl Ester - pharmacology</subject><subject>Nitric Oxide - physiology</subject><subject>Nitric Oxide Synthase - antagonists & inhibitors</subject><subject>Pharmacology. Drug treatments</subject><subject>Receptors, Lysosphingolipid - deficiency</subject><subject>Receptors, Lysosphingolipid - drug effects</subject><subject>Receptors, Lysosphingolipid - genetics</subject><subject>Receptors, Lysosphingolipid - physiology</subject><subject>Sphingosine - analogs & derivatives</subject><subject>Sphingosine - pharmacology</subject><subject>Sphingosine - physiology</subject><subject>Sphingosine - therapeutic use</subject><subject>Tumor Necrosis Factor-alpha - pharmacology</subject><subject>Vasodilator agents. Cerebral vasodilators</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFUM2O0zAQthCI7RZeAZkDnDZd_ySxfayqhVaqWATlXDnJuPEqtYPtrJQn4_Xw7hZxmdGMvp_5BqGPlKworentZvdj82u_Puzuv6236xUl1aomgvLqFVrQipVFWXH1Gi0IIaoQnLErdB3jQx5rLqq36IrWSjJVsgX6s7WnvujARZtmPNjRj8EnsC5i7TqcerABt97FZNMELt3gOPbWnXy0DgpajL3PC53gBnc2QJuGGT8rtOmJjHvQIWF90lkxYRvbHs5W3wYYIZgpWu-wdQ9TmHPDj_bR56KfmT_pd46HOfoXC59vsx3OFjAmH96hN0YPEd5f-hIdvtwdNttif_91t1nvi54qkQpNTUWFpE3bMCqI5NAqo5sWDJNAgJedMKYjjBLJNBNSViU3mijGOmWahi_R5xfZnOn3BDEdzzkDDIN24Kd4rKVUQuV3L9GHC3BqztAdx2DPOszHf5_OgE8XgI6tHkzQrrXxP07SupS05H8B9AuV8g</recordid><startdate>20060926</startdate><enddate>20060926</enddate><creator>THEILMEIER, Gregor</creator><creator>SCHMIDT, Christoph</creator><creator>SCHOBER, Otmar</creator><creator>HILDEBRAND, Reinhard</creator><creator>SCHULZ, Rainer</creator><creator>HEUSCH, Gerd</creator><creator>HAUDE, Michael</creator><creator>VON WNUCK LIPINSKI, Karin</creator><creator>HERZOG, Christine</creator><creator>SCHMITZ, Martina</creator><creator>ERBEL, Raimund</creator><creator>CHUN, Jerold</creator><creator>HERRMANN, Jörg</creator><creator>LEVKAU, Bodo</creator><creator>KEUL, Petra</creator><creator>SCHÄFERS, Michael</creator><creator>HERRGOTT, Ilka</creator><creator>MERSMANN, Jan</creator><creator>LARMANN, Jan</creator><creator>HERMANN, Sven</creator><creator>STYPMANN, Jörg</creator><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20060926</creationdate><title>High-density lipoproteins and their constituent, sphingosine-1-phosphate, directly protect the heart against ischemia/reperfusion injury in vivo via the S1P3 lysophospholipid receptor</title><author>THEILMEIER, Gregor ; SCHMIDT, Christoph ; SCHOBER, Otmar ; HILDEBRAND, Reinhard ; SCHULZ, Rainer ; HEUSCH, Gerd ; HAUDE, Michael ; VON WNUCK LIPINSKI, Karin ; HERZOG, Christine ; SCHMITZ, Martina ; ERBEL, Raimund ; CHUN, Jerold ; HERRMANN, Jörg ; LEVKAU, Bodo ; KEUL, Petra ; SCHÄFERS, Michael ; HERRGOTT, Ilka ; MERSMANN, Jan ; LARMANN, Jan ; HERMANN, Sven ; STYPMANN, Jörg</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h197t-a1f51781bcb217083ec9fabcef28e0e34d7ffd021082a2788543fa0922d9fbb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Antihypertensive agents</topic><topic>Apoptosis - drug effects</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Cardiotonic Agents - pharmacology</topic><topic>Cardiotonic Agents - therapeutic use</topic><topic>Cardiovascular system</topic><topic>Cell Adhesion - drug effects</topic><topic>Cells, Cultured - drug effects</topic><topic>Chemotaxis, Leukocyte - drug effects</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Endothelial Cells - drug effects</topic><topic>Endothelial Cells - physiology</topic><topic>Female</topic><topic>Humans</topic><topic>Lipoproteins, HDL - pharmacology</topic><topic>Lipoproteins, HDL - physiology</topic><topic>Lipoproteins, HDL - therapeutic use</topic><topic>Lipoproteins, LDL - pharmacology</topic><topic>Lysophospholipids - pharmacology</topic><topic>Lysophospholipids - physiology</topic><topic>Lysophospholipids - therapeutic use</topic><topic>Macrophages - physiology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Myocardial Ischemia - drug therapy</topic><topic>Myocardial Reperfusion Injury - prevention & control</topic><topic>Myocytes, Cardiac - drug effects</topic><topic>Myocytes, Cardiac - pathology</topic><topic>NG-Nitroarginine Methyl Ester - pharmacology</topic><topic>Nitric Oxide - physiology</topic><topic>Nitric Oxide Synthase - antagonists & inhibitors</topic><topic>Pharmacology. Drug treatments</topic><topic>Receptors, Lysosphingolipid - deficiency</topic><topic>Receptors, Lysosphingolipid - drug effects</topic><topic>Receptors, Lysosphingolipid - genetics</topic><topic>Receptors, Lysosphingolipid - physiology</topic><topic>Sphingosine - analogs & derivatives</topic><topic>Sphingosine - pharmacology</topic><topic>Sphingosine - physiology</topic><topic>Sphingosine - therapeutic use</topic><topic>Tumor Necrosis Factor-alpha - pharmacology</topic><topic>Vasodilator agents. 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We hypothesized that some of the cholesterol transport-independent biological properties of high-density lipoprotein (HDL) implied in atheroprotection may also be beneficial in settings of acute myocardial reperfusion injury.
In an in vivo mouse model of myocardial ischemia/reperfusion, we observed that HDL and its sphingolipid component, sphingosine-1-phosphate (S1P), dramatically attenuated infarction size by approximately 20% and 40%, respectively. The underlying mechanism was an inhibition of inflammatory neutrophil recruitment and cardiomyocyte apoptosis in the infarcted area. In vitro, HDL and S1P potently suppressed leukocyte adhesion to activated endothelium under flow and protected rat neonatal cardiomyocytes against apoptosis. In vivo, HDL- and S1P-mediated cardioprotection was dependent on nitric oxide (NO) and the S1P3 lysophospholipid receptor, because it was abolished by pharmacological NO synthase inhibition and was completely absent in S1P3-deficient mice.
Our data demonstrate that HDL and its constituent, S1P, acutely protect the heart against ischemia/reperfusion injury in vivo via an S1P3-mediated and NO-dependent pathway. A rapid therapeutic elevation of S1P-containing HDL plasma levels may be beneficial in patients at high risk of acute myocardial ischemia.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>16982942</pmid><doi>10.1161/CIRCULATIONAHA.105.607135</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0009-7322 |
| ispartof | Circulation (New York, N.Y.), 2006-09, Vol.114 (13), p.1403-1409 |
| issn | 0009-7322 1524-4539 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68897945 |
| source | MEDLINE; American Heart Association Journals; EZB-FREE-00999 freely available EZB journals; Journals@Ovid Complete |
| subjects | Animals Antihypertensive agents Apoptosis - drug effects Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Cardiotonic Agents - pharmacology Cardiotonic Agents - therapeutic use Cardiovascular system Cell Adhesion - drug effects Cells, Cultured - drug effects Chemotaxis, Leukocyte - drug effects Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Endothelial Cells - drug effects Endothelial Cells - physiology Female Humans Lipoproteins, HDL - pharmacology Lipoproteins, HDL - physiology Lipoproteins, HDL - therapeutic use Lipoproteins, LDL - pharmacology Lysophospholipids - pharmacology Lysophospholipids - physiology Lysophospholipids - therapeutic use Macrophages - physiology Male Medical sciences Mice Mice, Inbred C57BL Mice, Knockout Myocardial Ischemia - drug therapy Myocardial Reperfusion Injury - prevention & control Myocytes, Cardiac - drug effects Myocytes, Cardiac - pathology NG-Nitroarginine Methyl Ester - pharmacology Nitric Oxide - physiology Nitric Oxide Synthase - antagonists & inhibitors Pharmacology. Drug treatments Receptors, Lysosphingolipid - deficiency Receptors, Lysosphingolipid - drug effects Receptors, Lysosphingolipid - genetics Receptors, Lysosphingolipid - physiology Sphingosine - analogs & derivatives Sphingosine - pharmacology Sphingosine - physiology Sphingosine - therapeutic use Tumor Necrosis Factor-alpha - pharmacology Vasodilator agents. Cerebral vasodilators |
| title | High-density lipoproteins and their constituent, sphingosine-1-phosphate, directly protect the heart against ischemia/reperfusion injury in vivo via the S1P3 lysophospholipid receptor |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T22%3A42%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=High-density%20lipoproteins%20and%20their%20constituent,%20sphingosine-1-phosphate,%20directly%20protect%20the%20heart%20against%20ischemia/reperfusion%20injury%20in%20vivo%20via%20the%20S1P3%20lysophospholipid%20receptor&rft.jtitle=Circulation%20(New%20York,%20N.Y.)&rft.au=THEILMEIER,%20Gregor&rft.date=2006-09-26&rft.volume=114&rft.issue=13&rft.spage=1403&rft.epage=1409&rft.pages=1403-1409&rft.issn=0009-7322&rft.eissn=1524-4539&rft.coden=CIRCAZ&rft_id=info:doi/10.1161/CIRCULATIONAHA.105.607135&rft_dat=%3Cproquest_pubme%3E68897945%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=68897945&rft_id=info:pmid/16982942&rfr_iscdi=true |