Platelet-released extracellular vesicles: the effects of thrombin activation.
Atherosclerosis
Extracellular vesicles
Microvesicles
Platelets
Thrombin
Thrombosis
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
14 Mar 2022
14 Mar 2022
Historique:
received:
08
12
2021
accepted:
23
02
2022
revised:
17
02
2022
entrez:
15
3
2022
pubmed:
16
3
2022
medline:
18
3
2022
Statut:
epublish
Résumé
Platelets exert fundamental roles in thrombosis, inflammation, and angiogenesis, contributing to different pathologies from cardiovascular diseases to cancer. We previously reported that platelets release extracellular vesicles (pEVs) which contribute to thrombus formation. However, pEV composition remains poorly defined. Indeed, pEV quality and type, rather than quantity, may be relevant in intravascular cross-talk with either circulating or vascular cells. We aimed to define the phenotypic characteristics of pEVs released spontaneously and those induced by thrombin activation to better understand their role in disease dissemination. pEVs obtained from washed platelets from healthy donor blood were characterized by flow cytometry. pEVs from thrombin-activated platelets (T-pEVs) showed higher levels of P-selectin and active form of glycoprotein IIb/IIIa than baseline non-activated platelets (B-pEVs). Following mass spectrometry-based differential proteomic analysis, significant changes in the abundance of proteins secreted in T-pEVs compared to B-pEVs were found. These differential proteins were involved in coagulation, adhesion, cytoskeleton, signal transduction, metabolism, and vesicle-mediated transport. Interestingly, release of proteins relevant for cell adhesion, intrinsic pathway coagulation, and platelet activation signalling was significantly modified by thrombin stimulation. A novel pEV-associated protein (protocadherin-α4) was found to be significantly reduced in T-pEVs showing a shift towards increased expression in the membranes of activated platelets. In summary, platelet activation induced by thrombin triggers the shedding of pEVs with a complex proteomic pattern rich in procoagulant and proadhesive proteins. Crosstalk with other vascular and blood cells in a paracrine regulatory mode could extend the prothrombotic signalling as well as promote proteostasic changes in other cellular types.
Identifiants
pubmed: 35288766
doi: 10.1007/s00018-022-04222-4
pii: 10.1007/s00018-022-04222-4
pmc: PMC8920058
doi:
Substances chimiques
Proteins
0
Thrombin
EC 3.4.21.5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
190Subventions
Organisme : National Plan for Science and Innovation
ID : PID2019-107160RB-I00
Organisme : National Plan for Science and Innovation
ID : PGC2018-094025-B-I00
Organisme : Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares
ID : CB16/11/00411
Organisme : Instituto de Salud Carlos III
ID : FIS PI19/01687
Organisme : Departament d'Universitats, Recerca i Societat de la Informació
ID : 2017 SGR 1480
Organisme : Agència de Gestió d'Ajuts Universitaris i de Recerca
ID : 2019BP00211
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
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