Revealing Concealed Cardioprotection by Platelet Mfsd2b-released S1P in Human and Murine Myocardial Infarction

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Apr 26

PMID 37100836

Authors

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 Schroder

Petra Keul

Sarah Weske

Philipp Wollnitzke

Dragos Duse

Sureyya Saffak

Mareike Cramer

Florian Bonner

Tina Muller

Markus H Graler

Tobias Zeus

Malte Kelm

Bodo Levkau

Affiliations

Soon will be listed here.

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 (S1P). 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.

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