دورية أكاديمية
Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function
| العنوان: | Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function |
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| المؤلفون: | Yana Roka-Moiia, Kaitlyn R. Ammann, Samuel Miller-Gutierrez, Jawaad Sheriff, Danny Bluestein, Joseph E. Italiano, Robert C. Flaumenhaft, Marvin J. Slepian |
| المصدر: | International Journal of Molecular Sciences, Vol 24, Iss 8, p 7386 (2023) |
| بيانات النشر: | MDPI AG, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | platelet-derived microparticles, shear stress, adhesion receptors, agonist receptors, cardiovascular therapeutic devices, bleeding, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 24087386 1422-0067 1661-6596 |
| Relation: | https://www.mdpi.com/1422-0067/24/8/7386; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms24087386 |
| URL الوصول: | https://doaj.org/article/0b2d22ca8c0d43aea60f04217139354a |
| رقم الأكسشن: | edsdoj.0b2d22ca8c0d43aea60f04217139354a |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 24087386 14220067 16616596 |
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| DOI: | 10.3390/ijms24087386 |