Low shear stress-induced endothelial mesenchymal transformation via the down-regulation of TET2

Atherosclerotic cardiovascular disease is the major cause of death worldwide. Low shear stress plays key roles on the initiation and progression of atherosclerosis (As). However, its underlying mechanism remains unclear. In this study, the effect of low shear stress on endothelial mesenchymal transf...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical and biophysical research communications 2021-03, Vol.545, p.20-26
Main Authors: Li, AFang, Tan, LiLan, Zhang, ShuLei, Tao, Jun, Wang, Zuo, Wei, Dangheng
Format: Article
Language:English
Subjects:
Animals
Atherosclerosis
Atherosclerosis - etiology
Atherosclerosis - pathology
Atherosclerosis - prevention & control
DNA-Binding Proteins - antagonists & inhibitors
DNA-Binding Proteins - genetics
DNA-Binding Proteins - physiology
Down-Regulation
Endothelial mesenchymal transformation
Epithelial-Mesenchymal Transition - genetics
Epithelial-Mesenchymal Transition - physiology
Human Umbilical Vein Endothelial Cells
Humans
Low shear stress
Male
Mice
Mice, Knockout, ApoE
Proto-Oncogene Proteins - antagonists & inhibitors
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - physiology
RNA, Small Interfering - genetics
Stress, Mechanical
TET2
Up-Regulation
Vascular endothelial cells
Wnt Signaling Pathway
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Atherosclerotic cardiovascular disease is the major cause of death worldwide. Low shear stress plays key roles on the initiation and progression of atherosclerosis (As). However, its underlying mechanism remains unclear. In this study, the effect of low shear stress on endothelial mesenchymal transformation (EndMT) and its underlying mechanism were explored. Results showed that in cultured human umbilical vein endothelial cells, low shear stress down-regulated the expression of TET2 and promoted EndMT. Loss of TET2 promoted EndMT with the Wnt/β-catenin signaling pathway. The enhancement in EndMT induced by low shear stress was attenuated by TET2 overexpression. In apoE−/− mice subjected to carotid artery local ligation, the EndMT and atherosclerotic lesions induced by low shear stress was attenuated by TET2 overexpression. Taken together, low shear stress promoted EndMT through the down-regulation of TET2, indicating that intervention with EndMT or the up-regulation of TET2 might be an alternative strategy for preventing As. -Low shear stress-induced EndMT via the Wnt/β-catenin signaling pathway-Low shear stress down-regulated TET2 expression-TET2 overexpression inhibits low shear stress-induced EndMT and As
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2021.01.062