Oxidized low-density lipoprotein promotes vascular endothelial cell dysfunction by stimulating miR-496 expression and inhibiting the Hippo pathway effector YAP.

Cell Biology International
Jun HuFu Zhu

Abstract

Oxidized low-density lipoprotein (ox-LDL) can damage vascular endothelial cells and cause atherosclerosis, but its epigenetic regulatory mechanism has not been fully elucidated. We show that ox-LDL induced significant apoptosis and loss of function in human umbilical vascular endothelial cells (HUVECs). At the same time, ox-LDL significantly decreased the expression of Hippo-YAP/ZAP (Yes-associated protein/YLP motif-containing 1) pathway proteins as compared to that of the control. The luciferase reporter system confirmed that microRNA (miR)-496 silenced YAP gene expression by binding to its 3' untranslated region (3' UTR). Ox-LDL-treated miR-496 overexpression HUVECs had a higher apoptosis rate and more severe dysfunction compared to the control cells. This in-depth study shows that ox-LDL inhibits YAP protein expression by inducing miR-496 expression, leading to its inability to enter the nucleus, thereby losing its function as a transcriptional cofactor for activating the downstream genes. Our findings reveal that, through epigenetic modification, ox-LDL can inhibit the normal expression of Hippo-YAP/ZAP pathway proteins via miR-496 expression and induce vascular endothelial cell dysfunction.

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Citations

Feb 6, 2020·Experimental and Therapeutic Medicine·Jing YeJie Tong
Dec 31, 2019·Experimental and Therapeutic Medicine·Xinhao WangWei Guo
Jan 21, 2021·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Pengyang LiBin Wang
Sep 16, 2021·Critical Reviews in Clinical Laboratory Sciences·Anvarsadat KianmehrAbdolkarim Mahrooz

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Methods Mentioned

BETA
light microscopy
flow cytometry
PCR
Antibody Sampler
transfection
Assay

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