Activation of Nrf2 Attenuates Pulmonary Vascular Remodeling via Inhibiting Endothelial-to-Mesenchymal Transition: an Insight from a Plant Polyphenol

The endothelial-to-mesenchymal transition (EndMT) has been demonstrated to be involved in pulmonary vascular remodeling. It is partly attributed to oxidative and inflammatory stresses in endothelial cells. In current study, we conducted a series of experiments to clarify the effect of salvianolic ac...

Full description

Saved in:
Bibliographic Details
Published in:International journal of biological sciences 2017-01, Vol.13 (8), p.1067-1081
Main Authors: Chen, Yucai, Yuan, Tianyi, Zhang, Huifang, Yan, Yu, Wang, Danshu, Fang, Lianhua, Lu, Yang, Du, Guanhua
Format: Article
Language:English
Subjects:
Animals
Antioxidants
Blotting, Western
Caffeic Acids - pharmacology
Cell adhesion & migration
Cell Line
Cell migration
Cell Survival - drug effects
Endothelial cells
Enzyme-Linked Immunosorbent Assay
Epithelial-Mesenchymal Transition - drug effects
Heme
Heme oxygenase (decyclizing)
Humans
Hypertension
Hypertension, Pulmonary - metabolism
Immunohistochemistry
Inflammation
Lactates - pharmacology
Lung - cytology
Male
Mesenchyme
Monocrotaline
NF-E2-Related Factor 2 - metabolism
Oxidative stress
Oxygenase
Polyphenols - pharmacology
Pulmonary hypertension
Rats
Rats, Wistar
Reactive oxygen species
Reactive Oxygen Species - metabolism
Research Paper
Transforming growth factor-b1
Translocation
Vascular Remodeling - drug effects
Wound Healing - drug effects
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The endothelial-to-mesenchymal transition (EndMT) has been demonstrated to be involved in pulmonary vascular remodeling. It is partly attributed to oxidative and inflammatory stresses in endothelial cells. In current study, we conducted a series of experiments to clarify the effect of salvianolic acid A (SAA), a kind of polyphenol compound, in the process of EndMT in human pulmonary arterial endothelial cells and in vivo therapeutic efficacy on vascular remodeling in monocrotaline (MCT)-induced EndMT. EndMT was induced by TGFβ1 in human pulmonary arterial endothelial cells (HPAECs). SAA significantly attenuated EndMT, simultaneously inhibited cell migration and reactive oxygen species (ROS) formation. In MCT-induced pulmonary arterial hypertension (PAH) model, SAA improved vascular function, decreased TGFβ1 level and inhibited inflammation. Mechanistically, SAA stimulated Nrf2 translocation and subsequent heme oxygenase-1 (HO-1) up-regulation. The effect of SAA on EndMT in vitro was abolished by ZnPP, a HO-1 inhibitor. In conclusion, this study indicates a deleterious impact of oxidative stress on EndMT. Polyphenol antioxidant treatment may provide an adjunctive action to alleviate pulmonary vascular remodeling via inhibiting EndMT.
ISSN:1449-2288
1449-2288
DOI:10.7150/ijbs.20316