Circulating platelet-leukocyte mixed conjugates and platelet microparticles are potential markers of inflammation in the atherothrombotic disease. Epoprostenol is a synthetic salt of PGI2 (prostacyclin) clinically used in pulmonary hypertension and transplantation as a potent inhibitor of platelet aggregation. In this study the in vitro effect of this drug was investigated on the interaction of platelets with leukocytes and on markers of leukocyte and platelet activation, including platelet microparticle formation. The analyses were performed by flow cytometry on citrated whole blood collected from healthy subjects and challenged by a mixture of collagen-ADP. Preliminarily, the epoprostenol antiplatelet effect was confirmed by both aggregometry and PFA-100 and by evaluation of intraplatelet VASP phosphorylation. Epoprostenol, at nanomolar concentrations, prevented the formation of platelet mixed conjugates with PMN or monocytes, platelet PAC-1 and P-selectin expression and platelet microparticle generation. The reference drugs PGE1, aspirin and the novel ADP-receptor antagonist, cangrelor, were only effective at micromolar concentrations. No effect of epoprostenol was detected on leukocyte activation markers. Our data suggest a possible additional mechanism of action of epoprostenol in reducing the inflammatory cell contribution to pulmonary hypertension and thrombosis.
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http://dx.doi.org/10.1016/j.thromres.2011.05.010 | DOI Listing |
Int J Mol Sci
December 2024
Department of Hemostasis and Hemostatic Disorders, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.
COVID-19 and post-COVID (long COVID) are associated with thromboembolic complications; however, it is still not clear whether platelets play a leading role in this phenomenon. The platelet hyperreactivity could result from the direct interaction between platelets and viral elements or the response to inflammatory and prothrombotic factors released from blood and vessel cells following infection. The existing literature does not provide clear-cut answers, as the results determining platelet status vary according to methodology.
View Article and Find Full Text PDFPharmacol Rep
January 2025
Department of Neurology, Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Miller School of Medicine, 1600 NW 10th Ave RMSB #7046, Miami, FL, 33136, USA.
Background: Current therapies to treat excessive bleeding are associated with significant complications, which may outweigh their benefits. Red blood cell-derived microparticles (RMPs) are a promising hemostatic agent. Previous studies demonstrated that they reduce bleeding in animal models, correct coagulation defects in patient blood, and have an excellent safety profile.
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2025
Department of Biomedical Engineering, Translational Tissue Engineering Center, Johns Hopkins Translational ImmunoEngineering Center, and the Institute for Nanobiotechnology, Johns Hopkins School of Medicine, 400 N. Broadway, Smith Building 5017, Baltimore, Maryland 21231, United States.
Biomimetic particles that can replicate aspects of natural biological cell function are useful for advanced biological engineering applications. Engineering such particles requires mimicking the chemical complexity of the surface of biological cells, and this can be achieved by coating synthetic particles with naturally derived cell membranes. Past research has demonstrated the feasibility of utilizing cell membrane coatings from a variety of cell types to achieve extended blood circulation half-life.
View Article and Find Full Text PDFBiomicrofluidics
December 2024
Department of Biomedical Engineering, University of Houston, Houston, Texas 77204, USA.
J Vis Exp
November 2024
Department of Haematology, University Hospital of Bordeaux; Inserm U1034, Biology of Cardiovascular Disease.
Activated platelets promote coagulation primarily by exposing the procoagulant phospholipid phosphatidylserine (PS) on their outer membrane surfaces and releasing PS-expressing microvesicles that retain the original membrane architecture and cytoplasmic components of their originating cells. The accessibility of phosphatidylserine facilitates the binding of major coagulation factors, significantly amplifying the catalytic efficiency of coagulation enzymes, while microvesicle release acts as a pivotal mediator of intercellular signaling. Procoagulant platelets play a crucial role in clot stabilization during hemostasis, and their increased proportion in the bloodstream correlates with an increased risk of thrombosis.
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