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Pravastatin reduces plasma levels of extracellular vesicles in pregnancies at high risk of term preeclampsia

Introduction: Elevated plasma levels of extracellular vesicles have been associated with impaired placentation, angiogenesis imbalance, intravascular inflammation, and endothelial dysfunction in women with preeclampsia, thus suggesting that circulating vesicles may be a good therapeutic target for t...

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Autores principales: Santoyo, Jean Michell, Noguera, José Antonio, Avilés, Francisco, Hernández-Caselles, Trinidad, de Paco-Matallana, Catalina, Delgado, Juan Luis, Cuevas, Santiago, Llinás, M. Teresa, Hernández, Isabel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10323224/
https://www.ncbi.nlm.nih.gov/pubmed/37426825
http://dx.doi.org/10.3389/fphar.2023.1166123
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author Santoyo, Jean Michell
Noguera, José Antonio
Avilés, Francisco
Hernández-Caselles, Trinidad
de Paco-Matallana, Catalina
Delgado, Juan Luis
Cuevas, Santiago
Llinás, M. Teresa
Hernández, Isabel
author_facet Santoyo, Jean Michell
Noguera, José Antonio
Avilés, Francisco
Hernández-Caselles, Trinidad
de Paco-Matallana, Catalina
Delgado, Juan Luis
Cuevas, Santiago
Llinás, M. Teresa
Hernández, Isabel
author_sort Santoyo, Jean Michell
collection PubMed
description Introduction: Elevated plasma levels of extracellular vesicles have been associated with impaired placentation, angiogenesis imbalance, intravascular inflammation, and endothelial dysfunction in women with preeclampsia, thus suggesting that circulating vesicles may be a good therapeutic target for the treatment of the disease. Recently, statins have been considered a potential treatment for the prevention of preeclampsia because of their pleiotropic effects, including the improvement of endothelial dysfunction and inhibition of inflammatory responses. However, the effects of these drugs on circulating vesicles concentration in women at risk of preeclampsia have not been established. Herein, we aimed to assess the effects of pravastatin on circulating extracellular vesicle generation in women at high risk of term preeclampsia. Methods: In a sample of 68 singleton pregnant women participating in the multicenter, double-blind, placebo-controlled STATIN trial (Nº EducraCT 2016-005206-19 ISRCTN), 35 women received a placebo and 33 women received a 20 mg/day dose of pravastatin for approximately 3 weeks (from 35 to 37 weeks of gestation until delivery). Large extracellular vesicles were characterized and quantified by flow cytometry using annexin V and cell-specific antibodies directed against platelet, endothelial, leukocyte, and syncytiotrophoblast cell surface markers. Results: In women who received the placebo, a significant increase in the plasma levels of large extracellular vesicles from platelets (34%, p < 0.01), leukocytes (33%, p < 0.01), monocytes (60%, p < 0.01), endothelial cells (40%, p < 0.05), and syncytiotrophoblast cells (22%, p < 0.05) were observed. However, treatment with pravastatin significantly reduced the plasma levels of large extracellular vesicles from platelets (42%, p < 0.001), leukocytes (25%, p < 0.001), monocytes (61%, p < 0.001), endothelial cells (69%, p < 0.001), activated endothelial cells (55%, p < 0.001), and syncytiotrophoblast cells (44%, p < 0.001). Discussion: These results indicate that pravastatin reduces the levels of activated cell-derived membrane vesicles from the maternal vasculature, blood, and placental syncytiotrophoblast of women at high risk of term preeclampsia, suggesting that this statin may be beneficial in reducing endothelial dysfunction and pro-inflammatory and pro-coagulatory state characteristics of the disease.
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spelling pubmed-103232242023-07-07 Pravastatin reduces plasma levels of extracellular vesicles in pregnancies at high risk of term preeclampsia Santoyo, Jean Michell Noguera, José Antonio Avilés, Francisco Hernández-Caselles, Trinidad de Paco-Matallana, Catalina Delgado, Juan Luis Cuevas, Santiago Llinás, M. Teresa Hernández, Isabel Front Pharmacol Pharmacology Introduction: Elevated plasma levels of extracellular vesicles have been associated with impaired placentation, angiogenesis imbalance, intravascular inflammation, and endothelial dysfunction in women with preeclampsia, thus suggesting that circulating vesicles may be a good therapeutic target for the treatment of the disease. Recently, statins have been considered a potential treatment for the prevention of preeclampsia because of their pleiotropic effects, including the improvement of endothelial dysfunction and inhibition of inflammatory responses. However, the effects of these drugs on circulating vesicles concentration in women at risk of preeclampsia have not been established. Herein, we aimed to assess the effects of pravastatin on circulating extracellular vesicle generation in women at high risk of term preeclampsia. Methods: In a sample of 68 singleton pregnant women participating in the multicenter, double-blind, placebo-controlled STATIN trial (Nº EducraCT 2016-005206-19 ISRCTN), 35 women received a placebo and 33 women received a 20 mg/day dose of pravastatin for approximately 3 weeks (from 35 to 37 weeks of gestation until delivery). Large extracellular vesicles were characterized and quantified by flow cytometry using annexin V and cell-specific antibodies directed against platelet, endothelial, leukocyte, and syncytiotrophoblast cell surface markers. Results: In women who received the placebo, a significant increase in the plasma levels of large extracellular vesicles from platelets (34%, p < 0.01), leukocytes (33%, p < 0.01), monocytes (60%, p < 0.01), endothelial cells (40%, p < 0.05), and syncytiotrophoblast cells (22%, p < 0.05) were observed. However, treatment with pravastatin significantly reduced the plasma levels of large extracellular vesicles from platelets (42%, p < 0.001), leukocytes (25%, p < 0.001), monocytes (61%, p < 0.001), endothelial cells (69%, p < 0.001), activated endothelial cells (55%, p < 0.001), and syncytiotrophoblast cells (44%, p < 0.001). Discussion: These results indicate that pravastatin reduces the levels of activated cell-derived membrane vesicles from the maternal vasculature, blood, and placental syncytiotrophoblast of women at high risk of term preeclampsia, suggesting that this statin may be beneficial in reducing endothelial dysfunction and pro-inflammatory and pro-coagulatory state characteristics of the disease. Frontiers Media S.A. 2023-06-22 /pmc/articles/PMC10323224/ /pubmed/37426825 http://dx.doi.org/10.3389/fphar.2023.1166123 Text en Copyright © 2023 Santoyo, Noguera, Avilés, Hernández-Caselles, de Paco-Matallana, Delgado, Cuevas, Llinás and Hernández. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Santoyo, Jean Michell
Noguera, José Antonio
Avilés, Francisco
Hernández-Caselles, Trinidad
de Paco-Matallana, Catalina
Delgado, Juan Luis
Cuevas, Santiago
Llinás, M. Teresa
Hernández, Isabel
Pravastatin reduces plasma levels of extracellular vesicles in pregnancies at high risk of term preeclampsia
title Pravastatin reduces plasma levels of extracellular vesicles in pregnancies at high risk of term preeclampsia
title_full Pravastatin reduces plasma levels of extracellular vesicles in pregnancies at high risk of term preeclampsia
title_fullStr Pravastatin reduces plasma levels of extracellular vesicles in pregnancies at high risk of term preeclampsia
title_full_unstemmed Pravastatin reduces plasma levels of extracellular vesicles in pregnancies at high risk of term preeclampsia
title_short Pravastatin reduces plasma levels of extracellular vesicles in pregnancies at high risk of term preeclampsia
title_sort pravastatin reduces plasma levels of extracellular vesicles in pregnancies at high risk of term preeclampsia
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10323224/
https://www.ncbi.nlm.nih.gov/pubmed/37426825
http://dx.doi.org/10.3389/fphar.2023.1166123
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