Characterization of plasma-derived small extracellular vesicles indicates ongoing endothelial and platelet activation in patients with thrombotic antiphospholipid syndrome

Štok, Ula (author), Blokar, Elizabeta (author), Lenassi, Metka (author), Holcar, Marija (author), Frank Bertoncelj, Mojca (author), Erman, Andreja (author), Resnik, Nataša (author), Sodin-Šemrl, Snežna (author), Čučnik, Saša (author), Perdan-Pirkmajer, Katja (author), Ambrožič, Aleš (author), Žigon, Polona (author)

Antiphospholipid syndrome (APS) is a systemic autoimmune disease, characterized by thrombosis, obstetric complications and the presence of antiphospholipid antibodies (aPL), which drive endothelial injury and thrombophilia. Extracellular vesicles (EVs) have been implicated in endothelial and thrombotic pathologies. Here, we characterized the quantity, cellular origin and the surface expression of biologically active molecules in small EVs (sEVs) isolated from the plasma of thrombotic APS patients (n = 14), aPL-negative patients with idiopathic thrombosis (aPL-neg IT, n = 5) and healthy blood donors (HBD, n = 7). Nanoparticle tracking analysis showed similar sEV sizes (110–170 nm) between the groups, with an increased quantity of sEVs in patients with APS and aPLneg IT compared to HBD. MACSPlex analysis of 37 different sEV surface markers showed endothelial (CD31), platelet (CD41b and CD42a), leukocyte (CD45), CD8 lymphocyte and APC (HLA-ABC) cell-derived sEVs. Except for CD8, these molecules were comparably expressed in all study groups. sEVs from APS patients were specifically enriched in surface expression of CD62P, suggesting endothelial and platelet activation in APS. Additionally, APS patients exhibited increased CD133/1 expression compared to aPL-neg IT, suggesting endothelial damage in APS patients. These findings demonstrate enhanced shedding, and distinct biological properties of sEVs in thrombotic APS.

• Language: English
• Keywords: antiphospholipid syndrome, thrombosis, adhesion molecules, small extracellular vesicles, surface protein markers, endothelial activation, platelet activation
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy; MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2020
• Number of pages: 13 str.
• Numbering: Vol. 9, iss. 5, art. 1211
• PID: 20.500.12556/RUL-133736
• UDC: 616.1
• ISSN on article: 2073-4409
• DOI: 10.3390/cells9051211
• COBISS.SI-ID: 15921155
• Publication date in RUL: 13.12.2021

Record is a part of a journal

• Title: Cells
• Shortened title: Cells
• Publisher: MDPI
• ISSN: 2073-4409
• COBISS.SI-ID: 519958809

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 13.05.2020

Secondary language

• Language: Slovenian
• Keywords: antifosfolipidni sindrom, tromboza, adhezijske molekule