Sphingosine‐1‐phosphate improves outcome of no‐reflow acute myocardial infarction via sphingosine‐1‐phosphate receptor 1
Abstract Aims Therapeutic options targeting post‐ischaemic cardiac remodelling are sparse. The bioactive sphingolipid sphingosine‐1‐phosphate (S1P) reduces ischaemia/reperfusion injury. However, its impact on post‐ischaemic remodelling independently of its infarct size (IS)‐reducing effect is yet un...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-02-01
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| Series: | ESC Heart Failure |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ehf2.14176 |
| _version_ | 1797944803768401920 |
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| author | Amin Polzin Lisa Dannenberg Marcel Benkhoff Maike Barcik Petra Keul Aysel Ayhan Sarah Weske Samantha Ahlbrecht Kajetan Trojovsky Carolin Helten Sebastian Haberkorn Ulrich Flögel Tobias Zeus Tina Müller Markus H. Gräler Malte Kelm Bodo Levkau |
| author_facet | Amin Polzin Lisa Dannenberg Marcel Benkhoff Maike Barcik Petra Keul Aysel Ayhan Sarah Weske Samantha Ahlbrecht Kajetan Trojovsky Carolin Helten Sebastian Haberkorn Ulrich Flögel Tobias Zeus Tina Müller Markus H. Gräler Malte Kelm Bodo Levkau |
| author_sort | Amin Polzin |
| collection | DOAJ |
| description | Abstract Aims Therapeutic options targeting post‐ischaemic cardiac remodelling are sparse. The bioactive sphingolipid sphingosine‐1‐phosphate (S1P) reduces ischaemia/reperfusion injury. However, its impact on post‐ischaemic remodelling independently of its infarct size (IS)‐reducing effect is yet unknown and was addressed in this study. Methods and results Acute myocardial infarction (AMI) in mice was induced by permanent ligation of the left anterior descending artery (LAD). C57Bl6 were treated with the S1P lyase inhibitor 4‐deoxypyridoxine (DOP) starting 7 days prior to AMI to increase endogenous S1P concentrations. Cardiac function and myocardial healing were assessed by cardiovascular magnetic resonance imaging (cMRI), murine echocardiography, histomorphology, and gene expression analysis. DOP effects were investigated in cardiomyocyte‐specific S1P receptor 1 deficient (S1PR1 Cardio Cre+) and Cre− control mice and S1P concentrations measured by LC‐MS/MS. IS and cardiac function did not differ between control and DOP‐treated groups on day one after LAD‐ligation despite fourfold increase in plasma S1P. In contrast, cardiac function was clearly improved and myocardial scar size reduced, respectively, on Day 21 in DOP‐treated mice. The latter also exhibited smaller cardiomyocyte size and reduced embryonic gene expression. The benefit of DOP treatment was abolished in S1PR1 Cardio Cre+. Conclusions S1P improves cardiac function and myocardial healing post AMI independently of initial infarct size and accomplishes this via the cardiomyocyte S1PR1. Hence, in addition to its beneficial effects on I/R injury, S1PR1 may be a promising target in post‐infarction myocardial remodelling as adjunctive therapy to revascularization as well as in patients not eligible for standard interventional procedures. |
| first_indexed | 2024-04-10T20:45:25Z |
| format | Article |
| id | doaj.art-ff12a4b41a044c2dbe150ec1060b1b94 |
| institution | Directory Open Access Journal |
| issn | 2055-5822 |
| language | English |
| last_indexed | 2024-04-10T20:45:25Z |
| publishDate | 2023-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | ESC Heart Failure |
| spelling | doaj.art-ff12a4b41a044c2dbe150ec1060b1b942023-01-24T09:02:17ZengWileyESC Heart Failure2055-58222023-02-0110133434110.1002/ehf2.14176Sphingosine‐1‐phosphate improves outcome of no‐reflow acute myocardial infarction via sphingosine‐1‐phosphate receptor 1Amin Polzin0Lisa Dannenberg1Marcel Benkhoff2Maike Barcik3Petra Keul4Aysel Ayhan5Sarah Weske6Samantha Ahlbrecht7Kajetan Trojovsky8Carolin Helten9Sebastian Haberkorn10Ulrich Flögel11Tobias Zeus12Tina Müller13Markus H. Gräler14Malte Kelm15Bodo Levkau16Department of Cardiology, Pulmonary Diseases, and Vascular Medicine, Medical Faculty, CARID Cardiovascular Research Institute of Duesseldorf Heinrich Heine University of Duesseldorf Moorenstr. 5 40225 Düsseldorf GermanyDepartment of Cardiology, Pulmonary Diseases, and Vascular Medicine, Medical Faculty, CARID Cardiovascular Research Institute of Duesseldorf Heinrich Heine University of Duesseldorf Moorenstr. 5 40225 Düsseldorf GermanyDepartment of Cardiology, Pulmonary Diseases, and Vascular Medicine, Medical Faculty, CARID Cardiovascular Research Institute of Duesseldorf Heinrich Heine University of Duesseldorf Moorenstr. 5 40225 Düsseldorf GermanyDepartment of Cardiology, Pulmonary Diseases, and Vascular Medicine, Medical Faculty, CARID Cardiovascular Research Institute of Duesseldorf Heinrich Heine University of Duesseldorf Moorenstr. 5 40225 Düsseldorf GermanyInstitute of Molecular Medicine III, University Hospital Düsseldorf Heinrich Heine University Düsseldorf Düsseldorf GermanyDepartment of Cardiology, Pulmonary Diseases, and Vascular Medicine, Medical Faculty, CARID Cardiovascular Research Institute of Duesseldorf Heinrich Heine University of Duesseldorf Moorenstr. 5 40225 Düsseldorf GermanyInstitute of Molecular Medicine III, University Hospital Düsseldorf Heinrich Heine University Düsseldorf Düsseldorf GermanyDepartment of Cardiology, Pulmonary Diseases, and Vascular Medicine, Medical Faculty, CARID Cardiovascular Research Institute of Duesseldorf Heinrich Heine University of Duesseldorf Moorenstr. 5 40225 Düsseldorf GermanyDepartment of Cardiology, Pulmonary Diseases, and Vascular Medicine, Medical Faculty, CARID Cardiovascular Research Institute of Duesseldorf Heinrich Heine University of Duesseldorf Moorenstr. 5 40225 Düsseldorf GermanyDepartment of Cardiology, Pulmonary Diseases, and Vascular Medicine, Medical Faculty, CARID Cardiovascular Research Institute of Duesseldorf Heinrich Heine University of Duesseldorf Moorenstr. 5 40225 Düsseldorf GermanyDepartment of Cardiology, Pulmonary Diseases, and Vascular Medicine, Medical Faculty, CARID Cardiovascular Research Institute of Duesseldorf Heinrich Heine University of Duesseldorf Moorenstr. 5 40225 Düsseldorf GermanyDepartment of Molecular Cardiology Heinrich Heine University Düsseldorf GermanyDepartment of Cardiology, Pulmonary Diseases, and Vascular Medicine, Medical Faculty, CARID Cardiovascular Research Institute of Duesseldorf Heinrich Heine University of Duesseldorf Moorenstr. 5 40225 Düsseldorf GermanyDepartment of Anesthesiology and Intensive Care University Hospital Jena Jena GermanyDepartment of Anesthesiology and Intensive Care University Hospital Jena Jena GermanyDepartment of Cardiology, Pulmonary Diseases, and Vascular Medicine, Medical Faculty, CARID Cardiovascular Research Institute of Duesseldorf Heinrich Heine University of Duesseldorf Moorenstr. 5 40225 Düsseldorf GermanyInstitute of Molecular Medicine III, University Hospital Düsseldorf Heinrich Heine University Düsseldorf Düsseldorf GermanyAbstract Aims Therapeutic options targeting post‐ischaemic cardiac remodelling are sparse. The bioactive sphingolipid sphingosine‐1‐phosphate (S1P) reduces ischaemia/reperfusion injury. However, its impact on post‐ischaemic remodelling independently of its infarct size (IS)‐reducing effect is yet unknown and was addressed in this study. Methods and results Acute myocardial infarction (AMI) in mice was induced by permanent ligation of the left anterior descending artery (LAD). C57Bl6 were treated with the S1P lyase inhibitor 4‐deoxypyridoxine (DOP) starting 7 days prior to AMI to increase endogenous S1P concentrations. Cardiac function and myocardial healing were assessed by cardiovascular magnetic resonance imaging (cMRI), murine echocardiography, histomorphology, and gene expression analysis. DOP effects were investigated in cardiomyocyte‐specific S1P receptor 1 deficient (S1PR1 Cardio Cre+) and Cre− control mice and S1P concentrations measured by LC‐MS/MS. IS and cardiac function did not differ between control and DOP‐treated groups on day one after LAD‐ligation despite fourfold increase in plasma S1P. In contrast, cardiac function was clearly improved and myocardial scar size reduced, respectively, on Day 21 in DOP‐treated mice. The latter also exhibited smaller cardiomyocyte size and reduced embryonic gene expression. The benefit of DOP treatment was abolished in S1PR1 Cardio Cre+. Conclusions S1P improves cardiac function and myocardial healing post AMI independently of initial infarct size and accomplishes this via the cardiomyocyte S1PR1. Hence, in addition to its beneficial effects on I/R injury, S1PR1 may be a promising target in post‐infarction myocardial remodelling as adjunctive therapy to revascularization as well as in patients not eligible for standard interventional procedures.https://doi.org/10.1002/ehf2.14176CardioprotectionLAD‐ligationInfarct sizeRemodellingSphingosine‐1‐phosphate |
| spellingShingle | Amin Polzin Lisa Dannenberg Marcel Benkhoff Maike Barcik Petra Keul Aysel Ayhan Sarah Weske Samantha Ahlbrecht Kajetan Trojovsky Carolin Helten Sebastian Haberkorn Ulrich Flögel Tobias Zeus Tina Müller Markus H. Gräler Malte Kelm Bodo Levkau Sphingosine‐1‐phosphate improves outcome of no‐reflow acute myocardial infarction via sphingosine‐1‐phosphate receptor 1 ESC Heart Failure Cardioprotection LAD‐ligation Infarct size Remodelling Sphingosine‐1‐phosphate |
| title | Sphingosine‐1‐phosphate improves outcome of no‐reflow acute myocardial infarction via sphingosine‐1‐phosphate receptor 1 |
| title_full | Sphingosine‐1‐phosphate improves outcome of no‐reflow acute myocardial infarction via sphingosine‐1‐phosphate receptor 1 |
| title_fullStr | Sphingosine‐1‐phosphate improves outcome of no‐reflow acute myocardial infarction via sphingosine‐1‐phosphate receptor 1 |
| title_full_unstemmed | Sphingosine‐1‐phosphate improves outcome of no‐reflow acute myocardial infarction via sphingosine‐1‐phosphate receptor 1 |
| title_short | Sphingosine‐1‐phosphate improves outcome of no‐reflow acute myocardial infarction via sphingosine‐1‐phosphate receptor 1 |
| title_sort | sphingosine 1 phosphate improves outcome of no reflow acute myocardial infarction via sphingosine 1 phosphate receptor 1 |
| topic | Cardioprotection LAD‐ligation Infarct size Remodelling Sphingosine‐1‐phosphate |
| url | https://doi.org/10.1002/ehf2.14176 |
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