Prognostic implications and procoagulant activity of phosphatidylserine exposure of blood cells and microparticles in patients with atrial fibrillation treated with pulmonary vein isolation

Meng, Huan; Kou, Junjie; Ma, Ruishuang; Ding, Wenbo; Kou, Yan; Cao, Mingming; Dong, Zengxiang; Bi, Yang; Thatte, Hemant S.; Shi, Jialan

doi:10.3892/mmr.2017.7763

Cited by 12 publications

(5 citation statements)

References 37 publications

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“…Macrophages may help maintain the circulation of low PS-positive EVs in a healthy state. This finding is consistent with studies implicating elevated PS-exposing EVs as potential biomarkers for various human diseases [ 54 , 55 ], albeit further studies are needed to test this hypothesis.…”

Section: Discussionsupporting

confidence: 90%

Phosphatidylserine-Exposing Annexin A1-Positive Extracellular Vesicles: Potential Cancer Biomarkers

et al. 2023

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Under physiological conditions, phosphatidylserine (PS) predominantly localizes to the cytosolic leaflet of the plasma membrane of cells. During apoptosis, PS is exposed on the cell surface and serves as an “eat-me” signal for macrophages to prevent releasing self-immunogenic cellular components from dying cells which could potentially lead to autoimmunity. However, increasing evidence indicates that viable cells can also expose PS on their surface. Interestingly, tumor cell-derived extracellular vesicles (EVs) externalize PS. Recent studies have proposed PS-exposing EVs as a potential biomarker for the early detection of cancer and other diseases. However, there are confounding results regarding subtypes of PS-positive EVs, and knowledge of PS exposure on the EV surface requires further elucidation. In this study, we enriched small EVs (sEVs) and medium/large EVs (m/lEVs) from conditioned media of breast cancer cells (MDA-MB-231, MDA-MB-468) and non-cancerous cells (keratinocytes, fibroblasts). Since several PS-binding molecules are available to date, we compared recombinant proteins of annexin A5 and the carboxylated glutamic acid domain of Protein S (GlaS), also specific for PS, to detect PS-exposing EVs. Firstly, PS externalization in each EV fraction was analyzed using a bead-based EV assay, which combines EV capture using microbeads and analysis of PS-exposing EVs by flow cytometry. The bulk EV assay showed higher PS externalization in m/lEVs derived from MDA-MB-468 cells but not from MDA-MB-231 cells, while higher binding of GlaS was also observed in m/lEVs from fibroblasts. Second, using single EV flow cytometry, PS externalization was also analyzed on individual sEVs and m/lEVs. Significantly higher PS externalization was detected in m/lEVs (annexin A1+) derived from cancer cells compared to m/lEVs (annexin A1+) from non-cancerous cells. These results emphasize the significance of PS-exposing m/lEVs (annexin A1+) as an undervalued EV subtype for early cancer detection and provide a better understanding of PS externalization in disease-associated EV subtypes.

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Section: Discussionsupporting

confidence: 90%

Phosphatidylserine-Exposing Annexin A1-Positive Extracellular Vesicles: Potential Cancer Biomarkers

et al. 2023

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“…Macrophages may help maintain the circulation of low PS-positive EVs in a healthy state. This finding is consistent with studies implicating elevated PS-exposing EVs as potential biomarkers for various human diseases [52, 53], albeit further studies are needed to test this hypothesis.…”

Section: Discussionsupporting

confidence: 90%

Phosphatidylserine-exposing medium/large extracellular vesicles: potential cancer biomarkers

Perez

Bernard

Vocelle

et al. 2022

Preprint

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Under physiological conditions, phosphatidylserine (PS) predominantly localizes to the cytosolic leaflet of the plasma membrane of cells. During apoptosis, PS is exposed on the cell surface and serves as an eat-me signal for macrophages to prevent re-leasing self-immunogenic cellular components from dying cells which could potentially lead to autoimmunity. However, increasing evidence indicates that viable cells can also expose PS on their surface. Interestingly, tumor cell-derived extracellular vesicles (EVs) also externalize PS. Recent studies have proposed PS-exposing EVs as a potential biomarker for the early detection of cancer and other diseases. However, there are confounding results regarding subtypes of PS-positive EVs, and knowledge of PS exposure on the EV surface requires further elucidation. In this study, we enriched small EVs (sEVs) and medium/large EVs (m/lEVs) from conditioned media of breast cancer cells (MDA-MB-231, MDA-MB-468) and non-cancerous cells (keratinocytes, fibroblasts). Since several PS-binding molecules are available to date, we compared recombinant proteins of annexin A5 and the carboxylated glutamic acid domain of Protein S (GlaS), also specific for PS, to detect PS-exposing EVs. Firstly, PS externalization in each EV fraction was analyzed using a bead-based EV assay, which combines EV capture using microbeads and analysis of PS-exposing EVs by flow cytometry. The bulk EV assay showed higher PS externalization in m/lEVs derived from MDA-MB-468 cells but not from MDA-MB-231 cells, while higher binding of GlaS was also observed in m/lEVs from fibroblasts. Second, using single EV flow cytometry, PS externalization was also analyzed on individual sEVs and m/lEVs. Significantly higher PS externalization was detected in m/lEVs (annexin A1+) derived from cancer cells compared to m/lEVs (annexin A1+) from non-cancerous cells. These results emphasize the significance of PS-exposing m/lEVs as an undervalued EV subtype for early cancer detection and provide a better understanding of PS externalization in disease-associated EV subtypes.

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“…It was also proven that both endothelial-derived EVs (>355/μL) as well as leukocyte-derived EVs (>639/μL) were risk factors for the early recurrence of atrial fibrillation (ERAF). Additionally, the former were shown to be an independent predictor of the ERAF [ 45 ].…”

Section: Extracellular Vesicles In Patients With Atrial Fibrillationmentioning

confidence: 99%

Extracellular Vesicles in Atrial Fibrillation—State of the Art

Procyk

Bilicki

Balsam

et al. 2022

IJMS

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Extracellular vesicles are particles released from cells and delimited by a lipid bilayer. They have been widely studied, including extensive investigation in cardiovascular diseases. Many scientists have explored their role in atrial fibrillation. Patients suffering from atrial fibrillation have been evidenced to present altered levels of these particles as well as changed amounts of their contents such as micro-ribonucleic acids (miRs). Although many observations have been made so far, a large randomized clinical trial is needed to assess the previous findings. This review aims to thoroughly summarize current research regarding extracellular vesicles in atrial fibrillation.

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Prognostic implications and procoagulant activity of phosphatidylserine exposure of blood cells and microparticles in patients with atrial fibrillation treated with pulmonary vein isolation

Cited by 12 publications

References 37 publications

Phosphatidylserine-Exposing Annexin A1-Positive Extracellular Vesicles: Potential Cancer Biomarkers

Phosphatidylserine-Exposing Annexin A1-Positive Extracellular Vesicles: Potential Cancer Biomarkers

Phosphatidylserine-exposing medium/large extracellular vesicles: potential cancer biomarkers

Extracellular Vesicles in Atrial Fibrillation—State of the Art

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