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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...

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Autores principales: Zhang, Zhaosi, Zhao, Guosheng, Liu, Liu, He, Junchi, Darwazeh, Rami, Liu, Han, Chen, Hong, Zhou, Chao, Guo, Zongduo, Sun, Xiaochuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2019
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
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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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