Head-to-Head Comparison of Tissue Factor-Dependent Procoagulant Potential of Small and Large Extracellular Vesicles in Healthy Subjects and in Patients with SARS-CoV-2 Infection
The relative contribution of small (sEVs) and large extracellular vesicles (lEVs) to the total plasma procoagulant potential is not yet well defined. Thus, we compared total and TF<sup>pos</sup>-sEVs and -lEVs isolated from healthy subjects and COVID-19 patients during the acute phase of...
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MDPI AG
2023-09-01
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| Online Access: | https://www.mdpi.com/2079-7737/12/9/1233 |
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| author | Marta Brambilla Roberto Frigerio Alessia Becchetti Alessandro Gori Marina Cretich Maria Conti Antonella Mazza Martino Pengo Marina Camera |
| author_facet | Marta Brambilla Roberto Frigerio Alessia Becchetti Alessandro Gori Marina Cretich Maria Conti Antonella Mazza Martino Pengo Marina Camera |
| author_sort | Marta Brambilla |
| collection | DOAJ |
| description | The relative contribution of small (sEVs) and large extracellular vesicles (lEVs) to the total plasma procoagulant potential is not yet well defined. Thus, we compared total and TF<sup>pos</sup>-sEVs and -lEVs isolated from healthy subjects and COVID-19 patients during the acute phase of the infection and after symptom remission in terms of (1) vesicle enumeration using nanoparticle tracking assay, imaging flow cytometry, and TF immunofluorescence localization in a single-vesicle analysis using microarrays; (2) cellular origin; and (3) TF-dependent Xa generation capacity, as well as assessing the contribution of the TF inhibitor, TFPI. In healthy subjects, the plasma concentration of CD9/CD63/CD81<sup>pos</sup> sEVs was 30 times greater than that of calcein<sup>pos</sup> lEVs, and both were mainly released by platelets. Compared to lEVs, the levels of TF<sup>pos</sup>-sEVs were 2-fold higher. The TF-dependent Xa generation capacity of lEVs was three times greater than that of sEVs, with the latter being hindered by TFPI. Compared to HSs, the amounts of total and TF<sup>pos</sup>-sEVs and -lEVs were significantly greater in acute COVID-19 patients, which reverted to the physiological values at the 6-month follow-up. Interestingly, the FXa generation of lEVs only significantly increased during acute infection, with that of sEV being similar to that of HSs. Thus, in both healthy subjects and COVID-19 patients, the TF-dependent procoagulant potential is mostly sustained by large vesicles. |
| first_indexed | 2024-03-10T23:01:06Z |
| format | Article |
| id | doaj.art-17347c41dcac4e0fab19c31ebdba1ef9 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-10T23:01:06Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-17347c41dcac4e0fab19c31ebdba1ef92023-11-19T09:38:53ZengMDPI AGBiology2079-77372023-09-01129123310.3390/biology12091233Head-to-Head Comparison of Tissue Factor-Dependent Procoagulant Potential of Small and Large Extracellular Vesicles in Healthy Subjects and in Patients with SARS-CoV-2 InfectionMarta Brambilla0Roberto Frigerio1Alessia Becchetti2Alessandro Gori3Marina Cretich4Maria Conti5Antonella Mazza6Martino Pengo7Marina Camera8Centro Cardiologico Monzino IRCCS, 20138 Milan, ItalyNational Research Council of Italy (SCITEC-CNR), 20133 Milan, ItalyCentro Cardiologico Monzino IRCCS, 20138 Milan, ItalyNational Research Council of Italy (SCITEC-CNR), 20133 Milan, ItalyNational Research Council of Italy (SCITEC-CNR), 20133 Milan, ItalyCentro Cardiologico Monzino IRCCS, 20138 Milan, ItalyCentro Cardiologico Monzino IRCCS, 20138 Milan, ItalyIstituto Auxologico Italiano IRCCS, 20149 Milan, ItalyCentro Cardiologico Monzino IRCCS, 20138 Milan, ItalyThe relative contribution of small (sEVs) and large extracellular vesicles (lEVs) to the total plasma procoagulant potential is not yet well defined. Thus, we compared total and TF<sup>pos</sup>-sEVs and -lEVs isolated from healthy subjects and COVID-19 patients during the acute phase of the infection and after symptom remission in terms of (1) vesicle enumeration using nanoparticle tracking assay, imaging flow cytometry, and TF immunofluorescence localization in a single-vesicle analysis using microarrays; (2) cellular origin; and (3) TF-dependent Xa generation capacity, as well as assessing the contribution of the TF inhibitor, TFPI. In healthy subjects, the plasma concentration of CD9/CD63/CD81<sup>pos</sup> sEVs was 30 times greater than that of calcein<sup>pos</sup> lEVs, and both were mainly released by platelets. Compared to lEVs, the levels of TF<sup>pos</sup>-sEVs were 2-fold higher. The TF-dependent Xa generation capacity of lEVs was three times greater than that of sEVs, with the latter being hindered by TFPI. Compared to HSs, the amounts of total and TF<sup>pos</sup>-sEVs and -lEVs were significantly greater in acute COVID-19 patients, which reverted to the physiological values at the 6-month follow-up. Interestingly, the FXa generation of lEVs only significantly increased during acute infection, with that of sEV being similar to that of HSs. Thus, in both healthy subjects and COVID-19 patients, the TF-dependent procoagulant potential is mostly sustained by large vesicles.https://www.mdpi.com/2079-7737/12/9/1233small extracellular vesicleslarge extracellular vesiclestissue factorfactor Xa generationCOVID-19 |
| spellingShingle | Marta Brambilla Roberto Frigerio Alessia Becchetti Alessandro Gori Marina Cretich Maria Conti Antonella Mazza Martino Pengo Marina Camera Head-to-Head Comparison of Tissue Factor-Dependent Procoagulant Potential of Small and Large Extracellular Vesicles in Healthy Subjects and in Patients with SARS-CoV-2 Infection Biology small extracellular vesicles large extracellular vesicles tissue factor factor Xa generation COVID-19 |
| title | Head-to-Head Comparison of Tissue Factor-Dependent Procoagulant Potential of Small and Large Extracellular Vesicles in Healthy Subjects and in Patients with SARS-CoV-2 Infection |
| title_full | Head-to-Head Comparison of Tissue Factor-Dependent Procoagulant Potential of Small and Large Extracellular Vesicles in Healthy Subjects and in Patients with SARS-CoV-2 Infection |
| title_fullStr | Head-to-Head Comparison of Tissue Factor-Dependent Procoagulant Potential of Small and Large Extracellular Vesicles in Healthy Subjects and in Patients with SARS-CoV-2 Infection |
| title_full_unstemmed | Head-to-Head Comparison of Tissue Factor-Dependent Procoagulant Potential of Small and Large Extracellular Vesicles in Healthy Subjects and in Patients with SARS-CoV-2 Infection |
| title_short | Head-to-Head Comparison of Tissue Factor-Dependent Procoagulant Potential of Small and Large Extracellular Vesicles in Healthy Subjects and in Patients with SARS-CoV-2 Infection |
| title_sort | head to head comparison of tissue factor dependent procoagulant potential of small and large extracellular vesicles in healthy subjects and in patients with sars cov 2 infection |
| topic | small extracellular vesicles large extracellular vesicles tissue factor factor Xa generation COVID-19 |
| url | https://www.mdpi.com/2079-7737/12/9/1233 |
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