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

A. Polzin; L. Dannenberg; M. Benkhoff; M. Barcik; C. Helten; P. Mourikis; S. Ahlbrecht; L. Wildeis; J. Ziese; D. Zikeli; Daniel Metzen; H. Hu; L. Baensch; N. H. Schröder; P. Keul; S. Weske; P. Wollnitzke; D. Duse; S. Saffak; M. Cramer; F. Bönner; T. Müller; M. H. Gräler; T. Zeus; M. Kelm; B. Levkau

doi:10.1038/s41467-023-38069-5

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

A. Polzin, L. Dannenberg, M. Benkhoff, M. Barcik, C. Helten, P. Mourikis, S. Ahlbrecht, L. Wildeis, J. Ziese, D. Zikeli, Daniel Metzen, H. Hu, L. Baensch, N. H. Schröder, P. Keul, S. Weske, P. Wollnitzke, D. Duse, S. Saffak, M. CramerF. Bönner, T. Müller, M. H. Gräler, T. Zeus, M. Kelm, B. Levkau

Western Sydney University

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	2404
Number of pages	11
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-38069-5
Publication status	Published - Dec 2023

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Polzin, A., Dannenberg, L., Benkhoff, M., Barcik, M., Helten, C., Mourikis, P., Ahlbrecht, S., Wildeis, L., Ziese, J., Zikeli, D., Metzen, D., Hu, H., Baensch, L., Schröder, N. H., Keul, P., Weske, S., Wollnitzke, P., Duse, D., Saffak, S., ... Levkau, B. (2023). Revealing concealed cardioprotection by platelet Mfsd2b-released S1P in human and murine myocardial infarction. Nature Communications, 14(1), Article 2404. https://doi.org/10.1038/s41467-023-38069-5

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title = "Revealing concealed cardioprotection by platelet Mfsd2b-released S1P in human and murine myocardial infarction",

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.",

author = "A. Polzin and L. Dannenberg and M. Benkhoff and M. Barcik and C. Helten and P. Mourikis and S. Ahlbrecht and L. Wildeis and J. Ziese and D. Zikeli and Daniel Metzen and H. Hu and L. Baensch and Schr{\"o}der, {N. H.} and P. Keul and S. Weske and P. Wollnitzke and D. Duse and S. Saffak and M. Cramer and F. B{\"o}nner and T. M{\"u}ller and Gr{\"a}ler, {M. H.} and T. Zeus and M. Kelm and B. Levkau",

year = "2023",

month = dec,

doi = "10.1038/s41467-023-38069-5",

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journal = "Nature Communications",

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Polzin, A, Dannenberg, L, Benkhoff, M, Barcik, M, Helten, C, Mourikis, P, Ahlbrecht, S, Wildeis, L, Ziese, J, Zikeli, D, Metzen, D, Hu, H, Baensch, L, Schröder, NH, Keul, P, Weske, S, Wollnitzke, P, Duse, D, Saffak, S, Cramer, M, Bönner, F, Müller, T, Gräler, MH, Zeus, T, Kelm, M & Levkau, B 2023, 'Revealing concealed cardioprotection by platelet Mfsd2b-released S1P in human and murine myocardial infarction', Nature Communications, vol. 14, no. 1, 2404. https://doi.org/10.1038/s41467-023-38069-5

TY - JOUR

T1 - Revealing concealed cardioprotection by platelet Mfsd2b-released S1P in human and murine myocardial infarction

AU - Polzin, A.

AU - Dannenberg, L.

AU - Benkhoff, M.

AU - Barcik, M.

AU - Helten, C.

AU - Mourikis, P.

AU - Ahlbrecht, S.

AU - Wildeis, L.

AU - Ziese, J.

AU - Zikeli, D.

AU - Metzen, Daniel

AU - Hu, H.

AU - Baensch, L.

AU - Schröder, N. H.

AU - Keul, P.

AU - Weske, S.

AU - Wollnitzke, P.

AU - Duse, D.

AU - Saffak, S.

AU - Cramer, M.

AU - Bönner, F.

AU - Müller, T.

AU - Gräler, M. H.

AU - Zeus, T.

AU - Kelm, M.

AU - Levkau, B.

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

UR - https://hdl.handle.net/1959.7/uws:73948

U2 - 10.1038/s41467-023-38069-5

DO - 10.1038/s41467-023-38069-5

M3 - Article

SN - 2041-1723

VL - 14

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2404

ER -

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

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