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Oxidized low‐density lipoprotein promotes vascular endothelial cell dysfunction by stimulating miR‐496 expression and inhibiting the Hippo pathway effector YAP
- Source :
- Cell Biology International
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
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.
- Subjects :
- 0301 basic medicine
Untranslated region
Apoptosis
Protein Serine-Threonine Kinases
Epigenesis, Genetic
Mice
03 medical and health sciences
0302 clinical medicine
miR‐496
Gene expression
microRNA
Human Umbilical Vein Endothelial Cells
Animals
Humans
Hippo Signaling Pathway
Epigenetics
3' Untranslated Regions
Research Articles
Adaptor Proteins, Signal Transducing
Hippo signaling pathway
Chemistry
Effector
Endothelial Cells
YAP-Signaling Proteins
Cell Biology
General Medicine
Atherosclerosis
Phosphoproteins
Hippo–YAP/ZAP pathway
Up-Regulation
Cell biology
Lipoproteins, LDL
Mice, Inbred C57BL
Endothelial stem cell
MicroRNAs
030104 developmental biology
030220 oncology & carcinogenesis
vascular endothelial cell
oxidized low‐density lipoprotein
Research Article
Signal Transduction
Transcription Factors
Subjects
Details
- ISSN :
- 10958355 and 10656995
- Volume :
- 43
- Database :
- OpenAIRE
- Journal :
- Cell Biology International
- Accession number :
- edsair.doi.dedup.....a7aabdfef401e5eea2de271807f0b39a