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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...

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Autores principales: Gu, Ying, Feng, Yaling, Yu, Jinjin, Yuan, Hua, Yin, Yongxiang, Ding, Jian, Zhao, Jun, Xu, Yaohui, Xu, Jianjuan, Che, Haisha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
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.
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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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