Open AccessSustained expression of MCP‐1 induced low wall shear stress loading in conjunction with turbulent flow on endothelial cells of intracranial aneurysm
Author(s) -
Chu Cheng,
Xu Gang,
Li Xiaocong,
Duan Zuowei,
Tao Lihong,
Cai Hongxia,
Yang Ming,
Zhang Xinjiang,
Chen Bin,
Zheng Yanyu,
Shi Hongcan,
Li Xiaoyu
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15868
Subject(s) - umbilical vein , dna methylation , methylation , shear stress , microrna , dnmt1 , microbiology and biotechnology , western blot , dna methyltransferase , gene expression , biology , chemistry , dna , gene , materials science , biochemistry , in vitro , composite material
Shear stress was reported to regulate the expression of AC007362, but its underlying mechanisms remain to be explored. In this study, to isolate endothelial cells of blood vessels, unruptured and ruptured intracranial aneurysm (IA) tissues were collected from IA patients. Subsequently, quantitative real‐time PCR (qRT‐PCR), Western blot and luciferase assay were performed to investigate the relationships between AC007362, miRNAs‐493 and monocyte chemoattractant protein‐1 (MCP‐1) in human umbilical vein endothelial cells (HUVECs) exposed to shear stress. Reduced representation bisulphite sequencing (RRBS) was performed to assess the level of DNA methylation in AC007362 promoter. Accordingly, AC007362 and MCP‐1 were significantly up‐regulated while miR‐493 was significantly down‐regulated in HUVECs exposed to shear stress. AC007362 could suppress the miR‐493 expression and elevate the MCP‐1 expression, and miR‐493 was shown to respectively target AC007362 and MCP‐1 . Moreover, shear stress in HUVECs led to the down‐regulated DNA methyltransferase 1 (DNMT1), as well as the decreased DNA methylation level of AC007362 promoter. Similar results were also observed in ruptured IA tissues when compared with unruptured IA tissues. In conclusion, this study presented a deep insight into the operation of the regulatory network of AC007362, miR‐493 and MCP‐1 upon shear stress. Under shear stress, the expression of AC007362 was enhanced by the inhibited promoter DNA methylation, while the expression of MCP‐1 was enhanced by sponging the expression of miR‐493.