Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function
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 an...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/8/7386 |
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| author | Yana Roka-Moiia Kaitlyn R. Ammann Samuel Miller-Gutierrez Jawaad Sheriff Danny Bluestein Joseph E. Italiano Robert C. Flaumenhaft Marvin J. Slepian |
| author_facet | Yana Roka-Moiia Kaitlyn R. Ammann Samuel Miller-Gutierrez Jawaad Sheriff Danny Bluestein Joseph E. Italiano Robert C. Flaumenhaft Marvin J. Slepian |
| author_sort | Yana Roka-Moiia |
| collection | DOAJ |
| description | 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 (α<sub>IIb</sub>β<sub>3</sub>, GPIX, PECAM-1, P-selectin, and PSGL-1) and agonist receptors (P<sub>2</sub>Y<sub>12</sub> 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. |
| first_indexed | 2024-03-11T04:55:42Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:55:42Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0b2d22ca8c0d43aea60f04217139354a2023-11-17T19:39:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248738610.3390/ijms24087386Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic FunctionYana Roka-Moiia0Kaitlyn R. Ammann1Samuel Miller-Gutierrez2Jawaad Sheriff3Danny Bluestein4Joseph E. Italiano5Robert C. Flaumenhaft6Marvin J. Slepian7Sarver Heart Center, Departments of Medicine and Biomedical Engineering, University of Arizona, 1501 N Campbell Ave, Building 201E, Room 6139, Tucson, AZ 85724, USASarver Heart Center, Departments of Medicine and Biomedical Engineering, University of Arizona, 1501 N Campbell Ave, Building 201E, Room 6139, Tucson, AZ 85724, USASarver Heart Center, Departments of Medicine and Biomedical Engineering, University of Arizona, 1501 N Campbell Ave, Building 201E, Room 6139, Tucson, AZ 85724, USADepartment of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, USADepartment of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, USABoston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USABoston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USASarver Heart Center, Departments of Medicine and Biomedical Engineering, University of Arizona, 1501 N Campbell Ave, Building 201E, Room 6139, Tucson, AZ 85724, USAImplantable 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 (α<sub>IIb</sub>β<sub>3</sub>, GPIX, PECAM-1, P-selectin, and PSGL-1) and agonist receptors (P<sub>2</sub>Y<sub>12</sub> 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.https://www.mdpi.com/1422-0067/24/8/7386platelet-derived microparticlesshear stressadhesion receptorsagonist receptorscardiovascular therapeutic devicesbleeding |
| spellingShingle | Yana Roka-Moiia Kaitlyn R. Ammann Samuel Miller-Gutierrez Jawaad Sheriff Danny Bluestein Joseph E. Italiano Robert C. Flaumenhaft Marvin J. Slepian Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function International Journal of Molecular Sciences platelet-derived microparticles shear stress adhesion receptors agonist receptors cardiovascular therapeutic devices bleeding |
| title | Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function |
| title_full | Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function |
| title_fullStr | Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function |
| title_full_unstemmed | Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function |
| title_short | Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function |
| title_sort | shear mediated platelet microparticles demonstrate phenotypic heterogeneity as to morphology receptor distribution and hemostatic function |
| topic | platelet-derived microparticles shear stress adhesion receptors agonist receptors cardiovascular therapeutic devices bleeding |
| url | https://www.mdpi.com/1422-0067/24/8/7386 |
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