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

First Author  Polzin A Year  2023
Journal  Nat Commun Volume  14
Issue  1 Pages  2404
PubMed ID  37100836 Mgi Jnum  J:350043
Mgi Id  MGI:7468160 Doi  10.1038/s41467-023-38069-5
Citation  Polzin A, et al. (2023) Revealing concealed cardioprotection by platelet Mfsd2b-released S1P in human and murine myocardial infarction. Nat Commun 14(1):2404
abstractText  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(1)). 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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