Bexarotene Exerts Protective Effects Through Modulation of the Cerebral Vascular Smooth Muscle Cell Phenotypic Transformation by Regulating PPARγ/FLAP/LTB After Subarachnoid Hemorrhage in Rats.

Authors:
Guosheng Zhao
Guosheng Zhao
The Third Xiangya Hospital of Central South University
Changsha Shi | China
Liu Liu
Liu Liu
University of Toronto
United States
Junchi He
Junchi He
Nanjing First Hospital
Rami Darwazeh
Rami Darwazeh
The First Affiliated Hospital of Chongqing Medical University
China
Han Liu
Han Liu
Princeton University
Princeton | United States
Hong Chen
Hong Chen
Peking University People's Hospital
China
Chao Zhou
Chao Zhou
Institute of Medicinal Plant Development
New Delhi | India

Cell Transplant 2019 Apr 22:963689719842161. Epub 2019 Apr 22.

1 Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

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), 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 in VSMCs.

Download full-text PDF

Source
http://dx.doi.org/10.1177/0963689719842161DOI Listing
April 2019
8 Reads

Publication Analysis

Top Keywords

phenotypic transformation
16
cerebral cortical
12
neurological impairment
12
blood flow
12
cortical blood
12
improved cerebral
8
reduced neurological
8
impairment improved
8
vsmc phenotypic
8
subarachnoid hemorrhage
8
smooth muscle
8
inhibited vsmc
8
flow inhibited
8
bexarotene reduced
8
vascular smooth
8
transformation
5
vsmcs
5
cerebral
5
expression 5-lipoxygenase-activating
4
transformation cerebral
4

References

(Supplied by CrossRef)
Article in Transl Stroke Res
Fujii M et al.
Transl Stroke Res 2013
Article in Nat Rev Neurol
Zhang JH et al.
Nat Rev Neurol 2012
Article in Sci Rep
Zhang H et al.
Sci Rep 2017
Article in J Cereb Blood Flow Metab
Wan W et al.
J Cereb Blood Flow Metab 2018
Article in Science
Funk CD et al.
Science 2001
Article in Proc Natl Acad Sci U S A
Bäck M et al.
Proc Natl Acad Sci U S A 2005
Article in Trends Pharmacol Sci
Evans JF et al.
Trends Pharmacol Sci 2008
Article in Prostaglandins Leukot Essent Fatty Acids
Peters-Golden M et al.
Prostaglandins Leukot Essent Fatty Acids 2003
Article in Circ Res
Yu Z et al.
Circ Res 2013
Article in J Neurosci
Sobrado M et al.
J Neurosci 2009

Similar Publications