Structural characterization of platelets and platelet microvesicles

Пономарева, А. А.; Невзорова, Т. А.; Mordakhanova, Elmira R.; Andrianova, Izabella A.; Litvinov, Rustem I.

doi:10.1134/s1990519x1603010x

Cited by 9 publications

(14 citation statements)

References 24 publications

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“…This vesicles are likely pro-PDMPs or multivesicular PDMPs similar to those reported for thrombininduced activation. 103 35 The mechanodestruction mechanism is supported by prior modeling studies of membrane and whole cell shear stress accumulation, [108][109][110][111] and is consistent with our present TEM observations. In summary, our ultrastructural study of platelet microvesiculation following shear exposure allows us to conclude that (1) sheared platelets undergo shape change with cytoplasmic extrusion and pseudopodia extension; are crucial for platelet adhesion to vascular walls and aggregation to one another.…”

Section: Discussionsupporting

confidence: 91%

“…98,102 It was previously reported that similar morphological changes accompanied PDMP formation in response to activation by strong biochemical agonists. 103 Microvesiculation induced by thrombin and calcium ionophore was associated with filopodia formation, dilatation of the open canalicular system, degranulation, and cell defragmentation. [103][104][105] Our findings are also in agreement with previous studies of increased levels of shear.…”

Section: Discussionmentioning

confidence: 99%

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Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function

Roka‐Moiia

Ammann

Miller-Gutierrez

et al. 2023

Preprint

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Objective: Implantable cardiovascular therapeutic devices (CTD) including stents, percutaneous heart valves, and ventricular assist devices, while lifesaving, impart supraphysiologic shear stress to platelets resulting in thrombotic and bleeding device-related 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 shear-generated PDMPs manifest phenotypical heterogeneity of their morphology and surface expression of platelet receptors, and modulate platelet hemostatic function. Approach and Results: Human gel-filtered platelets were exposed to continuous shear stress and sonication. 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 in plasma was measured by optical aggregometry. We demonstrate that platelet exposure to shear stress promotes notable alterations in platelet morphology and ejection of several distinctive types of PDMPs. Shear-mediated microvesiculation is associated with the differential remodeling of platelet receptors with PDMPs expressing significantly higher levels of both adhesion receptors (αIIbβ3, GPIX, PECAM-1, P-selectin, and PSGL-1) and agonist-evoked receptors (P2Y12 & PAR1). Shear-mediated PDMPs have a bidirectional effect on platelet hemostatic function, promoting thrombin generation and inhibiting platelet aggregation induced by collagen and ADP. Conclusion: Shear-generated PDMPs demonstrate phenotypic heterogeneity as to morphologic features and defined patterns of surface receptor alteration 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.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function

Roka‐Moiia

Ammann

Miller-Gutierrez

et al. 2023

Preprint

View full text Add to dashboard Cite

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“…Thus, authors suggested that blood platelets cannot be exposed to high concentration of glatiramer acetate (500 µg/ml) in order to decrease side effects of glatiramer acetate injections. It was also proved that interfern beta 1a reduces the level of blood platelets, which results in greater susceptibility of MS patients to bleeding and brusining (Ponomareva et al 2016). Similarly fingolimod that is approved as a second-line treatment in MS rapidly decreases the number of blood platelets.…”

Section: Discussionmentioning

confidence: 99%

“…During activation of platelets microparticles (MPs) are released and are regard as a markers of platelet activation. Platelet MPs are the most abundant MPs found in the circulation (Badimon et al 2016, Ponomareva et al 2016, Papapanagiotou et al 2016, Boilard et al 2015, Varon et al 2015, and are potential mediators of blood coagulation by serving as circulating sources of tissue factor (TF) that is a transmembrane protein involved in thrombin generation. On the surface of MPs some quantity of phospatidylserine -a negatively charged aminophospholipid is exposed.…”

Section: Hemostatic Activity Of Blood Plateletsmentioning

confidence: 99%

The physiology of blood platelets and changes of their biological activities in multiple sclerosis

Wachowicz¹,

Morel²,

Miller³

et al. 2016

Acta Neurobiologiae Experimentalis

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Increasing evidence indicates that blood platelets contribute to diverse processes that extend beyond hemostasis. Many of the same mechanisms that play a role in hemostasis and thrombosis facilitate platelets the participation in other physiological and pathological processes, particularly in the inflammation, the immune response and central nervous system disorders. Platelets are involved in pathophysiology of central nervous system diseases, especially in the pathogenesis of multiple sclerosis, but their role appears to be neglected. Platelets contribute to the inflammation and cooperate with immune cells in inflammatory and immune responses. These blood cells were identified in inflamed spinal cord and in the brain in chronic active lesions of multiple sclerosis and in the related animal models referred as Experimental Autoimmune Encephalomyelitis. This review summarizes recent insights in the platelet activation accompanied by the exocytosis of bioactive compounds stored in granules, formation of platelet microparticles, expression of specific membrane receptors, synthesis of numerous biomediators, generation of free radicals, and introduces the mechanisms by which activated platelets may be involved in the pathophysiology of multiple sclerosis. Understanding the role of platelets in multiple sclerosis may be essential for improved therapies.

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“…Although several studies have been conducted, the exact mechanism of elevated tumour and PLT‐derived EV numbers, and formation of EVs originating from PLTs in healthy subjects remains unknown . The unfavourable tumour microenvironment, which includes hypoxia, acidosis and starvation, is thought to lead to autophagy of tumour cells and consequently to the elevated EV concentrations …”

Section: Discussionmentioning

confidence: 99%

Concentration of extracellular vesicles isolated from blood relative to the clinical pathological status of dogs with mast cell tumours

Šimundić¹,

Švara

Štukelj

et al. 2019

Vet Comparative Oncology

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Extracellular vesicles (EVs) are membrane-enclosed fragments shed from all cell types, including tumour cells. EVs contain a wide range of proteins, biolipids and genetic material derived from mother cells and therefore may be potential biomarkers for tumour diagnosis, disease progression and treatment success. We studied the effect of canine mast cell tumours (MCTs) on EV concentrations in blood isolates in association with MCT's histological grade, Ki-67 proliferative index, KITstaining pattern and number of PLT. The average EV concentration in blood isolates from nine dogs with MCTs was considerably higher than that in blood from eight healthy dogs. But there were no statistically significant differences in EVs concentration in the population of dogs with MCT according to a different histological grade of malignancy (Patnaik, Kiupel), KIT-staining pattern and Ki-67 proliferation index. The results show that these variables statistically do not significantly predicted EV concentrations in blood isolates (P > .05), except the KIT-staining pattern I which added statistically significantly to the prediction (P < .05). The results confirmed the impact of neoplasms on the morphological changes to cell membranes, which result in greater vesiculability and higher EV concentrations. K E Y W O R D S canine, extracellular vesicles, mast cell tumour, oncology, small animal

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Structural characterization of platelets and platelet microvesicles

Cited by 9 publications

References 24 publications

Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function

Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function

The physiology of blood platelets and changes of their biological activities in multiple sclerosis

Concentration of extracellular vesicles isolated from blood relative to the clinical pathological status of dogs with mast cell tumours

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