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Fasudil attenuates soluble fms-like tyrosine kinase-1 (sFlt-1)-induced hypertension in pregnant mice through RhoA/ROCK pathway
Preeclampsia (PE) has become the leading cause of maternal and fetal morbidity and mortality in the world, which is characterized by a systemic maternal inflammatory response associated with endothelial dysfunction, hypertension, and proteinuria. The development of PE is still barely predictable and...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732790/ https://www.ncbi.nlm.nih.gov/pubmed/29262624 http://dx.doi.org/10.18632/oncotarget.22017 |
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author | Gu, Ying Feng, Yaling Yu, Jinjin Yuan, Hua Yin, Yongxiang Ding, Jian Zhao, Jun Xu, Yaohui Xu, Jianjuan Che, Haisha |
author_facet | Gu, Ying Feng, Yaling Yu, Jinjin Yuan, Hua Yin, Yongxiang Ding, Jian Zhao, Jun Xu, Yaohui Xu, Jianjuan Che, Haisha |
author_sort | Gu, Ying |
collection | PubMed |
description | Preeclampsia (PE) has become the leading cause of maternal and fetal morbidity and mortality in the world, which is characterized by a systemic maternal inflammatory response associated with endothelial dysfunction, hypertension, and proteinuria. The development of PE is still barely predictable and thus challenging to prevent and manage clinically. Fasudil (FSD), the first-generation Rho/ROCK inhibitor, has been studied widely and applied in clinical practice with high safety and efficacy in treating hypertension and other cardiovascular diseases. However, few studies have focused on the effect of fasudil on preeclampsia in vivo and in vitro. Therefore, the aim of this study is to investigate the effects of fasudil on hypoxia/reoxygenation injury in vitro and its role on preeclamptic animal model. Here, we found that RhoA/ROCK pathway was significantly activated in H/R-challenged endothelial cells and in placenta and umbilical vessel of PE mice. And fasudil pre-treatment can protect vascular endothelial cells from H/R-induced apoptosis. In addition, inhibition of RhoA/ROCK pathway with fasudil can reduce the high blood pressure and urine protein levels as well as the concentration of s-Flt in peripheral and umbilical blood in a dose-dependent manner, thus resulting in prevention of the development of PE. Thus, Fasudil attenuates soluble fms-like tyrosine kinase-1 (sFlt-1)-induced hypertension in pregnant mice through RhoA/ROCK pathway, which would become a potential strategy for PE therapy. |
format | Online Article Text |
id | pubmed-5732790 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-57327902017-12-19 Fasudil attenuates soluble fms-like tyrosine kinase-1 (sFlt-1)-induced hypertension in pregnant mice through RhoA/ROCK pathway Gu, Ying Feng, Yaling Yu, Jinjin Yuan, Hua Yin, Yongxiang Ding, Jian Zhao, Jun Xu, Yaohui Xu, Jianjuan Che, Haisha Oncotarget Research Paper Preeclampsia (PE) has become the leading cause of maternal and fetal morbidity and mortality in the world, which is characterized by a systemic maternal inflammatory response associated with endothelial dysfunction, hypertension, and proteinuria. The development of PE is still barely predictable and thus challenging to prevent and manage clinically. Fasudil (FSD), the first-generation Rho/ROCK inhibitor, has been studied widely and applied in clinical practice with high safety and efficacy in treating hypertension and other cardiovascular diseases. However, few studies have focused on the effect of fasudil on preeclampsia in vivo and in vitro. Therefore, the aim of this study is to investigate the effects of fasudil on hypoxia/reoxygenation injury in vitro and its role on preeclamptic animal model. Here, we found that RhoA/ROCK pathway was significantly activated in H/R-challenged endothelial cells and in placenta and umbilical vessel of PE mice. And fasudil pre-treatment can protect vascular endothelial cells from H/R-induced apoptosis. In addition, inhibition of RhoA/ROCK pathway with fasudil can reduce the high blood pressure and urine protein levels as well as the concentration of s-Flt in peripheral and umbilical blood in a dose-dependent manner, thus resulting in prevention of the development of PE. Thus, Fasudil attenuates soluble fms-like tyrosine kinase-1 (sFlt-1)-induced hypertension in pregnant mice through RhoA/ROCK pathway, which would become a potential strategy for PE therapy. Impact Journals LLC 2017-10-24 /pmc/articles/PMC5732790/ /pubmed/29262624 http://dx.doi.org/10.18632/oncotarget.22017 Text en Copyright: © 2017 Gu et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Gu, Ying Feng, Yaling Yu, Jinjin Yuan, Hua Yin, Yongxiang Ding, Jian Zhao, Jun Xu, Yaohui Xu, Jianjuan Che, Haisha Fasudil attenuates soluble fms-like tyrosine kinase-1 (sFlt-1)-induced hypertension in pregnant mice through RhoA/ROCK pathway |
title | Fasudil attenuates soluble fms-like tyrosine kinase-1 (sFlt-1)-induced hypertension in pregnant mice through RhoA/ROCK pathway |
title_full | Fasudil attenuates soluble fms-like tyrosine kinase-1 (sFlt-1)-induced hypertension in pregnant mice through RhoA/ROCK pathway |
title_fullStr | Fasudil attenuates soluble fms-like tyrosine kinase-1 (sFlt-1)-induced hypertension in pregnant mice through RhoA/ROCK pathway |
title_full_unstemmed | Fasudil attenuates soluble fms-like tyrosine kinase-1 (sFlt-1)-induced hypertension in pregnant mice through RhoA/ROCK pathway |
title_short | Fasudil attenuates soluble fms-like tyrosine kinase-1 (sFlt-1)-induced hypertension in pregnant mice through RhoA/ROCK pathway |
title_sort | fasudil attenuates soluble fms-like tyrosine kinase-1 (sflt-1)-induced hypertension in pregnant mice through rhoa/rock pathway |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732790/ https://www.ncbi.nlm.nih.gov/pubmed/29262624 http://dx.doi.org/10.18632/oncotarget.22017 |
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