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Oxidized phospholipids on plasminogen influence platelet activation and reactivity

https://doi.org/10.1007/s00392-025-02625-4

Alexander Kille (Bad Krozingen)1, K. Kaier (Freiburg im Breisgau)2, T. Nührenberg (Bad Krozingen)3, K. Franke (Bad Krozingen)3, C. M. Valina (Bad Krozingen)3, X. Yang (La Jolla)4, G. Leibundgut (Basel)5, F.-J. Neumann (Bad Krozingen)1, D. Westermann (Freiburg im Breisgau)6, W. Hochholzer (Würzburg)7, S. Tsimikas (La Jolla)4

1Universitäts-Herzzentrum Freiburg / Bad Krozingen Klinik für Kardiologie und Angiologie Bad Krozingen, Deutschland; 2Universitätsklinikum Freiburg Institut für Medizinische Biometrie und Statistik Freiburg im Breisgau, Deutschland; 3Universitäts-Herzzentrum Freiburg / Bad Krozingen Klinik für Kardiologie und Angiologie II Bad Krozingen, Deutschland; 4University of California Vascular Medicine Program, Sulpizio Cardiovascular Center La Jolla, USA; 5Universitätsspital Basel Abt. für Kardiologie Basel, Schweiz; 6Universitäts-Herzzentrum Freiburg - Bad Krozingen Innere Medizin III, Kardiologie und Angiologie Freiburg im Breisgau, Deutschland; 7Klinikum Würzburg Mitte gGmbH Kardiologie & Internistische Intensivmedizin Würzburg, Deutschland

 

Background: Oxidized phospholipids (OxPL) on plasminogen (OxPL-PLG) are associated with reduced time to fibrinolysis and lower risk of cardiovascular outcomes, but it is not known if they influence platelet function.

Objectives: To evaluate the association of OxPL-PLG with intrinsic and on‑clopidogrel platelet reactivity and long-term cardiovascular events.

Methods: OxPL-PLG was measured in 2040 patients undergoing elective coronary angiography with or without percutaneous coronary angiography (PCI) if indicated in the EXCELSIOR trial. The association of OxPL-PLG to intrinsic and on-clopidogrel platelet reactivity and platelet surface expression of CD62P, CD41 and PAC-1 levels and to myocardial infarction(MI)-free survival and all-cause mortality at a median of 7 years using multivariable Cox regression models was determined.

Results: Elevated levels of OxPL-PLG were inversely and significantly associated with age, male sex, previous MI, PCI, and CABG, and positively will LDL-C, hypertension and obesity, plasminogen levels, platelet count and higher LV function. A significant association were present between OxPL-PLG and intrinsic platelet reactivity in response to ADP (p<0.001) but not collagen (p=0.085). OxPL-PLG was inversely and significantly associated with CD41 (p<0.001), CD62P (p<0.001), PAC-1 (p<0.001) platelet surface expression at baseline and with CD41 (p<0.001), CD62P (p=0.020), after 24 hours but not PAC-1 (p=0.058), p-values for linear relationship. OxPL-PLG and plasminogen were not associated with all-cause of MI-free survival at median 7-year follow-up.
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