Nature Communications (Apr 2023)
Revealing concealed cardioprotection by platelet Mfsd2b-released S1P in human and murine myocardial infarction
- Amin Polzin,
- Lisa Dannenberg,
- Marcel Benkhoff,
- Maike Barcik,
- Carolin Helten,
- Philipp Mourikis,
- Samantha Ahlbrecht,
- Laura Wildeis,
- Justus Ziese,
- Dorothee Zikeli,
- Daniel Metzen,
- Hao Hu,
- Leonard Baensch,
- Nathalie H. Schröder,
- Petra Keul,
- Sarah Weske,
- Philipp Wollnitzke,
- Dragos Duse,
- Süreyya Saffak,
- Mareike Cramer,
- Florian Bönner,
- Tina Müller,
- Markus H. Gräler,
- Tobias Zeus,
- Malte Kelm,
- Bodo Levkau
Affiliations
- Amin Polzin
- Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
- Lisa Dannenberg
- Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
- Marcel Benkhoff
- Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
- Maike Barcik
- Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
- Carolin Helten
- Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
- Philipp Mourikis
- Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
- Samantha Ahlbrecht
- Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
- Laura Wildeis
- Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
- Justus Ziese
- Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
- Dorothee Zikeli
- Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
- Daniel Metzen
- Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
- Hao Hu
- Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
- Leonard Baensch
- Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
- Nathalie H. Schröder
- Institute of Molecular Medicine III, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf
- Petra Keul
- Institute of Molecular Medicine III, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf
- Sarah Weske
- Institute of Molecular Medicine III, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf
- Philipp Wollnitzke
- Institute of Molecular Medicine III, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf
- Dragos Duse
- Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
- Süreyya Saffak
- Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
- Mareike Cramer
- Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
- Florian Bönner
- Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
- Tina Müller
- Department of Anesthesiology and Intensive Care, University Hospital Jena
- Markus H. Gräler
- Department of Anesthesiology and Intensive Care, University Hospital Jena
- Tobias Zeus
- Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
- Malte Kelm
- Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
- Bodo Levkau
- Institute of Molecular Medicine III, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf
- DOI
- https://doi.org/10.1038/s41467-023-38069-5
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 11
Abstract
Abstract Antiplatelet medication is standard of care in acute myocardial infarction (AMI). However, it may have obscured beneficial properties of the activated platelet secretome. We identify platelets as major source of a sphingosine-1-phosphate (S1P) burst during AMI, and find its magnitude to favorably associate with cardiovascular mortality and infarct size in STEMI patients over 12 months. Experimentally, administration of supernatant from activated platelets reduces infarct size in murine AMI, which is blunted in platelets deficient for S1P export (Mfsd2b) or production (Sphk1) and in mice deficient for cardiomyocyte S1P receptor 1 (S1P1). Our study reveals an exploitable therapeutic window in antiplatelet therapy in AMI as the GPIIb/IIIa antagonist tirofiban preserves S1P release and cardioprotection, whereas the P2Y12 antagonist cangrelor does not. Here, we report that platelet-mediated intrinsic cardioprotection is an exciting therapeutic paradigm reaching beyond AMI, the benefits of which may need to be considered in all antiplatelet therapies.
