Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function
Author
Roka-Moiia, Y.Ammann, K.R.
Miller-Gutierrez, S.
Sheriff, J.
Bluestein, D.
Italiano, J.E.
Flaumenhaft, R.C.
Slepian, M.J.
Affiliation
Sarver Heart Center, Departments of Medicine and Biomedical Engineering, University of ArizonaIssue Date
2023-04-17Keywords
adhesion receptorsagonist receptors
bleeding
cardiovascular therapeutic devices
platelet-derived microparticles
shear stress
thrombosis
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Roka-Moiia, Y.; Ammann, K.R.; Miller-Gutierrez, S.; Sheriff, J.; Bluestein, D.; Italiano, J.E.; Flaumenhaft, R.C.; Slepian, M.J. Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function. Int. J. Mol. Sci. 2023, 24, 7386. https://doi.org/10.3390/ijms24087386Rights
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
Implantable Cardiovascular Therapeutic Devices (CTD), while lifesaving, impart supraphysiologic shear stress to platelets, resulting in thrombotic and bleeding coagulopathy. We previously demonstrated that shear-mediated platelet dysfunction is associated with downregulation of platelet GPIb-IX-V and αIIbβ3 receptors via generation of Platelet-Derived MicroParticles (PDMPs). Here, we test the hypothesis that sheared PDMPs manifest phenotypical heterogeneity of morphology and receptor surface expression and modulate platelet hemostatic function. Human gel-filtered platelets were exposed to continuous shear stress. Alterations of platelet morphology were visualized using transmission electron microscopy. Surface expression of platelet receptors and PDMP generation were quantified by flow cytometry. Thrombin generation was quantified spectrophotometrically, and platelet aggregation was measured by optical aggregometry. Shear stress promotes notable alterations in platelet morphology and ejection of distinctive types of PDMPs. Shear-mediated microvesiculation is associated with the remodeling of platelet receptors, with PDMPs expressing significantly higher levels of adhesion receptors (αIIbβ3, GPIX, PECAM-1, P-selectin, and PSGL-1) and agonist receptors (P2Y12 and PAR1). Sheared PDMPs promote thrombin generation and inhibit platelet aggregation induced by collagen and ADP. Sheared PDMPs demonstrate phenotypic heterogeneity as to morphology and defined patterns of surface receptors and impose a bidirectional effect on platelet hemostatic function. PDMP heterogeneity suggests that a range of mechanisms are operative in the microvesiculation process, contributing to CTD coagulopathy and posing opportunities for therapeutic manipulation. © 2023 by the authors.Note
Open access journalISSN
1661-6596PubMed ID
37108551Version
Final Published Versionae974a485f413a2113503eed53cd6c53
10.3390/ijms24087386
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Except where otherwise noted, this item's license is described as © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license.
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