Antiplatelet Agents Inhibit the Generation of Platelet-Derived Microparticles
نویسندگان
چکیده
Platelet microparticles (PMPs) contribute to thrombogenesis but the effects of antiplatelet drugs on PMPs generation is undefined. The present study investigated the cellular events regulating PMPs shedding, testing in vitro platelet agonists and inhibitors. Platelet-rich plasma from healthy subjects was stimulated with arachidonic acid (AA), U46619, collagen type-I (10 and 1.5 μg/mL), epinephrine, ADP or TRAP-6 and pre-incubated with acetylsalicylic acid (ASA, 100 and 10 μmol/L), SQ-29,548, apyrase, PSB-0739, or eptifibatide. PMPs were detected by flow-cytometry using CD61 and annexin-V as fluorescent markers. Platelet agonists induced annexin V-positive PMPs shedding. The strongest response was to high concentration collagen. ADP-triggered PMPs shedding was dose-independent. ASA reduced PMPs induced by AA- (645, 347-2946 vs. 3061, 446-4901 PMPs/μL; median ad range, n = 9, P < 0.001), collagen 10 μg/mL (5317, 2027-15935 vs. 10252, 4187-46316 PMPs/μL; n = 13, P < 0.001), collagen 1.5 μg/mL (1078, 528-2820 vs. 1465, 582-5948 PMPs/μL; n = 21, P < 0.001) and TRAP-6 (2008, 1621-2495 vs. 2840, 2404-3031 PMPs/μL; n = 3, P < 0.01) but did not affect the response to epinephrine or ADP. The ADP scavenger apyrase reduced PMPs induced by U46619 (1256, 395-2908 vs. 3045, 1119-5494 PMPs/μL, n = 6, P < 0.05), collagen 1.5 μg/mL (1006, 780-1309 vs. 2422, 1839-3494 PMPs/μL, n = 3, P < 0.01) and TRAP-6 (904, 761-1224 vs. 2840, 2404-3031 PMPs/μL, n = 3, P < 0.01). The TP receptor antagonist SQ-29,548 and the P2Y12 receptor antagonist PSB-0739 markedly inhibited PMPs induced by low doses of collagen. Except for high-dose collagen, eptifibatide abolished agonist-induced PMPs release. Both TXA2 generation and ADP secretion are required as amplifiers of PMP shedding. The crucial role of the fibrinogen receptor and the collagen receptor in PMPs generation, independently of platelet aggregation, was identified.
منابع مشابه
An Overview on Platelet-derived Microparticles in Platelet Concentrates: blood collection, method preparation and storage
Preparations of platelet concentrates (PCs) that are stored under blood bank conditions and used for transfusion purposes, appear to be enriched in platelet derived-microparticles (PMPs) with high coagulant activity that may change platelet efficacy and safety issues. High shear stress could cause shedding of PMPs from the platelet plasma membrane, platelet aggregation, and activation of the co...
متن کاملEvaluation of microRNAs; mir223, mir222 and mir92a levels in the Platelet-derived microparticles in the Platelet concentrates produced by Platelet Rich Plasma method during storage
Abstract Background and Objectives Platelets release microparticles containing cellular components, including microRNAs, during storage. Assessment of these microRNAs is one of the markers for evaluation of platelet storage lesions. The aim of the present study was to evaluate the level of changes in the expression of mir-223, mir-92a and mir-222 during storage in platelets prepared by platele...
متن کاملPlatelet-derived Microparticles increase the Expression of hTERT Gene in Umbilical Cord Mesenchymal Stem Cells
Background: Mesenchymal stem cells have been widely considered in clinical researches because of their self-renewality and differentiation into various tissues. Nevertheless, their limited in vitro life span, which occurs only after several divisions, makes some changes in these cells, which affects all of their characteristics and remarkably reduces their application. In this study, the effect...
متن کاملSynthesis of N-arylmethyl Substituted Indole Derivatives as New Antiplatelet Aggregation Agents
A number of N-arylmethyl substituted indole derivatives have been synthesized and their effectiveness against ADP and arachidonic acid induced platelet aggregation in human plasma was determined. The desired compounds were synthesized by reacting the appropriate aniline derivative with isatin (or substituted isatin) to form the corresponding imine structures. The so formed compound was then act...
متن کاملInhibition of platelet-mediated, tissue factor-induced thrombin generation by the mouse/human chimeric 7E3 antibody. Potential implications for the effect of c7E3 Fab treatment on acute thrombosis and "clinical restenosis".
The murine/human chimeric monoclonal antibody fragment (c7E3 Fab) blocks GPIIb/IIIa and alpha v beta 3 receptors, inhibits platelet aggregation, and decreases the frequency of ischemic events after coronary artery angioplasty in patients at high risk of suffering such events. Although inhibition of platelet aggregation is likely to be the major mechanism of c7E3 Fab's effects, since activated p...
متن کامل