miR-21-5p/203a-3p promote ox-LDL-induced endothelial cell senescence through down-regulation of mitochondrial fission protein Drp1.
Mech Ageing Dev
; 164: 8-19, 2017 06.
Article
in En
| MEDLINE
| ID: mdl-28347692
ABSTRACT
This study aims to identify both endothelia-specific/enriched and senescence-associated miRNAs as well as their functions. The rats were fed on high-fat diet to establish a hyperlipidemic model, which showed an increase in plasma lipids and acceleration in endothelial senescence and endothelial dysfunction, accompanied by alterations in 7 endothelia-specific/enriched and senescence-associated miRNAs. Among the 7 selected miRNAs, miR-21-5p and miR-203a-3p were significantly up-regulated in a human umbilical vein endothelial cells (HUVECs) senescent model induced by ox-LDL, consistent with their changes in the hyperlipidemic rats. After performing the bioinformatic analysis, dynamin-related protein 1 (Drp1) was predicted to be a potential target for both miR-21-5p and miR-203a-3p. In ox-LDL-induced senescent HUVECs, Drp1 was significantly down-regulated, concomitant with mitochondrial dysfunctions and the activation of AMPK-p53/p16 pathway, while these phenomena were attenuated by miR-21-5p or miR-203a-3p inhibitor. Luciferase reporter gene assay confirmed a direct interaction between miR-21-5p and Drp1 but not between miR-203a-3p and Drp1. Based on these observations, we conclude that miR-21-5p/203a-3p promote ox-LDL-induced endothelial senescence through down-regulation of Drp1 in a direct or indirect way. Our findings highlight the plasma levels of miR-21-5p/203a-3p may serve as novel biomarkers to evaluate the degree of endothelial senescence in hyperlipidemia.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Down-Regulation
/
Cellular Senescence
/
Mitochondrial Proteins
/
Dynamins
/
MicroRNAs
/
Human Umbilical Vein Endothelial Cells
/
GTP Phosphohydrolases
/
Lipoproteins, LDL
/
Microtubule-Associated Proteins
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Mech Ageing Dev
Year:
2017
Document type:
Article
Affiliation country:
China