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Revealing concealed cardioprotection by platelet Mfsd2b-released S1P in human and murine myocardial infarction

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Listed:
  • Amin Polzin

    (University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
    Medical Faculty and University Hospital
    Imperial College London)

  • Lisa Dannenberg

    (University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf)

  • Marcel Benkhoff

    (University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf)

  • Maike Barcik

    (University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf)

  • Carolin Helten

    (University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf)

  • Philipp Mourikis

    (University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf)

  • Samantha Ahlbrecht

    (University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf)

  • Laura Wildeis

    (University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf)

  • Justus Ziese

    (University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf)

  • Dorothee Zikeli

    (University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf)

  • Daniel Metzen

    (University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf)

  • Hao Hu

    (University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf)

  • Leonard Baensch

    (University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf)

  • Nathalie H. Schröder

    (University Hospital Düsseldorf, Heinrich Heine University Düsseldorf)

  • Petra Keul

    (University Hospital Düsseldorf, Heinrich Heine University Düsseldorf)

  • Sarah Weske

    (University Hospital Düsseldorf, Heinrich Heine University Düsseldorf)

  • Philipp Wollnitzke

    (University Hospital Düsseldorf, Heinrich Heine University Düsseldorf)

  • Dragos Duse

    (University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
    University Hospital Düsseldorf, Heinrich Heine University Düsseldorf)

  • Süreyya Saffak

    (University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf)

  • Mareike Cramer

    (University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf)

  • Florian Bönner

    (University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
    Medical Faculty and University Hospital)

  • Tina Müller

    (University Hospital Jena)

  • Markus H. Gräler

    (University Hospital Jena)

  • Tobias Zeus

    (University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
    Medical Faculty and University Hospital)

  • Malte Kelm

    (University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf
    Medical Faculty and University Hospital)

  • Bodo Levkau

    (University Hospital Düsseldorf, Heinrich Heine University Düsseldorf)

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.

Suggested Citation

  • Amin Polzin & Lisa Dannenberg & Marcel Benkhoff & Maike Barcik & Carolin Helten & Philipp Mourikis & Samantha Ahlbrecht & Laura Wildeis & Justus Ziese & Dorothee Zikeli & Daniel Metzen & Hao Hu & Leon, 2023. "Revealing concealed cardioprotection by platelet Mfsd2b-released S1P in human and murine myocardial infarction," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38069-5
    DOI: 10.1038/s41467-023-38069-5
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    References listed on IDEAS

    as
    1. Thiet M. Vu & Ayako-Nakamura Ishizu & Juat Chin Foo & Xiu Ru Toh & Fangyu Zhang & Ding Ming Whee & Federico Torta & Amaury Cazenave-Gassiot & Takayoshi Matsumura & Sangho Kim & Sue-Anne E. S. Toh & To, 2017. "Mfsd2b is essential for the sphingosine-1-phosphate export in erythrocytes and platelets," Nature, Nature, vol. 550(7677), pages 524-528, October.
    2. Madhuvanthi Chandrakanthan & Toan Quoc Nguyen & Zafrul Hasan & Sneha Muralidharan & Thiet Minh Vu & Aaron Wei Liang Li & Uyen Thanh Nha Le & Hoa Thuy Ha & Sang-Ha Baik & Sock Hwee Tan & Juat Chin Foo , 2021. "Deletion of Mfsd2b impairs thrombotic functions of platelets," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
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