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Bexarotene Exerts Protective Effects Through Modulation of the Cerebral Vascular Smooth Muscle Cell Phenotypic Transformation by Regulating PPARγ/FLAP/LTB(4) After Subarachnoid Hemorrhage in Rats
Vascular smooth muscle cells (VSMCs) play an important role after a subarachnoid hemorrhage (SAH). The changes in VSMCs following bexarotene treatment after SAH are unknown. In the present study, neurological impairment, decreased cerebral cortical blood flow and transformation of cerebral VSMCs fro...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767892/ https://www.ncbi.nlm.nih.gov/pubmed/31010302 http://dx.doi.org/10.1177/0963689719842161 |
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author | Zhang, Zhaosi Zhao, Guosheng Liu, Liu He, Junchi Darwazeh, Rami Liu, Han Chen, Hong Zhou, Chao Guo, Zongduo Sun, Xiaochuan |
author_facet | Zhang, Zhaosi Zhao, Guosheng Liu, Liu He, Junchi Darwazeh, Rami Liu, Han Chen, Hong Zhou, Chao Guo, Zongduo Sun, Xiaochuan |
author_sort | Zhang, Zhaosi |
collection | PubMed |
description | Vascular smooth muscle cells (VSMCs) play an important role after a subarachnoid hemorrhage (SAH). The changes in VSMCs following bexarotene treatment after SAH are unknown. In the present study, neurological impairment, decreased cerebral cortical blood flow and transformation of cerebral VSMCs from a contractile to a synthetic phenotype were observed after SAH. Bexarotene reduced neurological impairment, improved cerebral cortical blood flow, inhibited VSMC phenotypic transformation and suppressed the expression of 5-lipoxygenase-activating protein (FLAP) and leukotriene B4 (LTB(4)), which was partly reversed by GW9662, an inhibitor of peroxisome proliferator-activated receptor gamma (PPARγ). Mechanistically, sh-PPARγ-mediated phenotypic transformation of VSMCs was partially suppressed by MK886, an antagonist of FLAP. Therefore, we conclude that bexarotene reduced neurological impairment, improved cerebral cortical blood flow and inhibited the VSMC phenotypic transformation after SAH, which was achieved by activating PPARγ-mediated inhibition of FLAP/LTB(4) in VSMCs |
format | Online Article Text |
id | pubmed-6767892 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-67678922019-10-18 Bexarotene Exerts Protective Effects Through Modulation of the Cerebral Vascular Smooth Muscle Cell Phenotypic Transformation by Regulating PPARγ/FLAP/LTB(4) After Subarachnoid Hemorrhage in Rats Zhang, Zhaosi Zhao, Guosheng Liu, Liu He, Junchi Darwazeh, Rami Liu, Han Chen, Hong Zhou, Chao Guo, Zongduo Sun, Xiaochuan Cell Transplant Original Articles Vascular smooth muscle cells (VSMCs) play an important role after a subarachnoid hemorrhage (SAH). The changes in VSMCs following bexarotene treatment after SAH are unknown. In the present study, neurological impairment, decreased cerebral cortical blood flow and transformation of cerebral VSMCs from a contractile to a synthetic phenotype were observed after SAH. Bexarotene reduced neurological impairment, improved cerebral cortical blood flow, inhibited VSMC phenotypic transformation and suppressed the expression of 5-lipoxygenase-activating protein (FLAP) and leukotriene B4 (LTB(4)), which was partly reversed by GW9662, an inhibitor of peroxisome proliferator-activated receptor gamma (PPARγ). Mechanistically, sh-PPARγ-mediated phenotypic transformation of VSMCs was partially suppressed by MK886, an antagonist of FLAP. Therefore, we conclude that bexarotene reduced neurological impairment, improved cerebral cortical blood flow and inhibited the VSMC phenotypic transformation after SAH, which was achieved by activating PPARγ-mediated inhibition of FLAP/LTB(4) in VSMCs SAGE Publications 2019-04-22 2019-09 /pmc/articles/PMC6767892/ /pubmed/31010302 http://dx.doi.org/10.1177/0963689719842161 Text en © The Author(s) 2019 http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Articles Zhang, Zhaosi Zhao, Guosheng Liu, Liu He, Junchi Darwazeh, Rami Liu, Han Chen, Hong Zhou, Chao Guo, Zongduo Sun, Xiaochuan Bexarotene Exerts Protective Effects Through Modulation of the Cerebral Vascular Smooth Muscle Cell Phenotypic Transformation by Regulating PPARγ/FLAP/LTB(4) After Subarachnoid Hemorrhage in Rats |
title | Bexarotene Exerts Protective Effects Through Modulation of the Cerebral
Vascular Smooth Muscle Cell Phenotypic Transformation by Regulating
PPARγ/FLAP/LTB(4) After Subarachnoid Hemorrhage in Rats |
title_full | Bexarotene Exerts Protective Effects Through Modulation of the Cerebral
Vascular Smooth Muscle Cell Phenotypic Transformation by Regulating
PPARγ/FLAP/LTB(4) After Subarachnoid Hemorrhage in Rats |
title_fullStr | Bexarotene Exerts Protective Effects Through Modulation of the Cerebral
Vascular Smooth Muscle Cell Phenotypic Transformation by Regulating
PPARγ/FLAP/LTB(4) After Subarachnoid Hemorrhage in Rats |
title_full_unstemmed | Bexarotene Exerts Protective Effects Through Modulation of the Cerebral
Vascular Smooth Muscle Cell Phenotypic Transformation by Regulating
PPARγ/FLAP/LTB(4) After Subarachnoid Hemorrhage in Rats |
title_short | Bexarotene Exerts Protective Effects Through Modulation of the Cerebral
Vascular Smooth Muscle Cell Phenotypic Transformation by Regulating
PPARγ/FLAP/LTB(4) After Subarachnoid Hemorrhage in Rats |
title_sort | bexarotene exerts protective effects through modulation of the cerebral
vascular smooth muscle cell phenotypic transformation by regulating
pparγ/flap/ltb(4) after subarachnoid hemorrhage in rats |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767892/ https://www.ncbi.nlm.nih.gov/pubmed/31010302 http://dx.doi.org/10.1177/0963689719842161 |
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