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Procoagulant Extracellular Vesicles Alter Trophoblast Differentiation in Mice by a Thrombo-Inflammatory Mechanism
Procoagulant extracellular vesicles (EV) and platelet activation have been associated with gestational vascular complications. EV-induced platelet-mediated placental inflammasome activation has been shown to cause preeclampsia-like symptoms in mice. However, the effect of EV-mediated placental throm...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466022/ https://www.ncbi.nlm.nih.gov/pubmed/34576036 http://dx.doi.org/10.3390/ijms22189873 |
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author | Markmeyer, Paulina Lochmann, Franziska Singh, Kunal Kumar Gupta, Anubhuti Younis, Ruaa Shahzad, Khurrum Biemann, Ronald Huebner, Hanna Ruebner, Matthias Isermann, Berend Kohli, Shrey |
author_facet | Markmeyer, Paulina Lochmann, Franziska Singh, Kunal Kumar Gupta, Anubhuti Younis, Ruaa Shahzad, Khurrum Biemann, Ronald Huebner, Hanna Ruebner, Matthias Isermann, Berend Kohli, Shrey |
author_sort | Markmeyer, Paulina |
collection | PubMed |
description | Procoagulant extracellular vesicles (EV) and platelet activation have been associated with gestational vascular complications. EV-induced platelet-mediated placental inflammasome activation has been shown to cause preeclampsia-like symptoms in mice. However, the effect of EV-mediated placental thrombo-inflammation on trophoblast differentiation remains unknown. Here, we identify that the EV-induced thrombo-inflammatory pathway modulates trophoblast morphology and differentiation. EVs and platelets reduce syncytiotrophoblast differentiation while increasing giant trophoblast and spongiotrophoblast including the glycogen-rich cells. These effects are platelet-dependent and mediated by the NLRP3 inflammasome. In humans, inflammasome activation was negatively correlated with trophoblast differentiation marker GCM1 and positively correlated with blood pressure. These data identify a crucial role of EV-induced placental thrombo-inflammation on altering trophoblast differentiation and suggest platelet activation or inflammasome activation as a therapeutic target in order to achieve successful placentation. |
format | Online Article Text |
id | pubmed-8466022 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84660222021-09-27 Procoagulant Extracellular Vesicles Alter Trophoblast Differentiation in Mice by a Thrombo-Inflammatory Mechanism Markmeyer, Paulina Lochmann, Franziska Singh, Kunal Kumar Gupta, Anubhuti Younis, Ruaa Shahzad, Khurrum Biemann, Ronald Huebner, Hanna Ruebner, Matthias Isermann, Berend Kohli, Shrey Int J Mol Sci Article Procoagulant extracellular vesicles (EV) and platelet activation have been associated with gestational vascular complications. EV-induced platelet-mediated placental inflammasome activation has been shown to cause preeclampsia-like symptoms in mice. However, the effect of EV-mediated placental thrombo-inflammation on trophoblast differentiation remains unknown. Here, we identify that the EV-induced thrombo-inflammatory pathway modulates trophoblast morphology and differentiation. EVs and platelets reduce syncytiotrophoblast differentiation while increasing giant trophoblast and spongiotrophoblast including the glycogen-rich cells. These effects are platelet-dependent and mediated by the NLRP3 inflammasome. In humans, inflammasome activation was negatively correlated with trophoblast differentiation marker GCM1 and positively correlated with blood pressure. These data identify a crucial role of EV-induced placental thrombo-inflammation on altering trophoblast differentiation and suggest platelet activation or inflammasome activation as a therapeutic target in order to achieve successful placentation. MDPI 2021-09-13 /pmc/articles/PMC8466022/ /pubmed/34576036 http://dx.doi.org/10.3390/ijms22189873 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Markmeyer, Paulina Lochmann, Franziska Singh, Kunal Kumar Gupta, Anubhuti Younis, Ruaa Shahzad, Khurrum Biemann, Ronald Huebner, Hanna Ruebner, Matthias Isermann, Berend Kohli, Shrey Procoagulant Extracellular Vesicles Alter Trophoblast Differentiation in Mice by a Thrombo-Inflammatory Mechanism |
title | Procoagulant Extracellular Vesicles Alter Trophoblast Differentiation in Mice by a Thrombo-Inflammatory Mechanism |
title_full | Procoagulant Extracellular Vesicles Alter Trophoblast Differentiation in Mice by a Thrombo-Inflammatory Mechanism |
title_fullStr | Procoagulant Extracellular Vesicles Alter Trophoblast Differentiation in Mice by a Thrombo-Inflammatory Mechanism |
title_full_unstemmed | Procoagulant Extracellular Vesicles Alter Trophoblast Differentiation in Mice by a Thrombo-Inflammatory Mechanism |
title_short | Procoagulant Extracellular Vesicles Alter Trophoblast Differentiation in Mice by a Thrombo-Inflammatory Mechanism |
title_sort | procoagulant extracellular vesicles alter trophoblast differentiation in mice by a thrombo-inflammatory mechanism |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466022/ https://www.ncbi.nlm.nih.gov/pubmed/34576036 http://dx.doi.org/10.3390/ijms22189873 |
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