LncRNA PVT1 knockdown alleviated ox-LDL-induced vascular endothelial cell injury and atherosclerosis by miR-153-3p/GRB2 axis via ERK/p38 pathway.
Nutr Metab Cardiovasc Dis
; 31(12): 3508-3521, 2021 11 29.
Article
em En
| MEDLINE
| ID: mdl-34627697
ABSTRACT
BACKGROUND AND AIMS:
LncRNA plasmacytoma variant translocation 1 (PVT1) plays a regulatory role in some cardiovascular diseases, but its role in atherosclerosis (AS) remains barely explored. The study aimed to investigate the effects of PVT1 on high fat diet-induced AS and its potential mechanisms. METHODS ANDRESULTS:
ApoE -/- mice were fed with high fat diet for 8 weeks to establish an AS model. Lentiviral vectors containing PVT1 short hairpin RNA (PVT1-shRNA) or NC-shRNA were administered by tail vein injection. Cell viability, apoptosis, inflammatory factor secretion, and cellular oxidative stress were measured to evaluate oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cell (HUVEC) injury. Dual-luciferase reporter gene and RNA immunoprecipitation assays were used to confirm the interaction between miR-153-3p and PVT1 or growth factor receptor binding protein 2 (GRB2). Atherosclerotic lesions, lipid deposition, and cell apoptosis in aorta were analyzed by H&E, Oil Red O, and TUNEL straining. PVT1 knockdown alleviated ox-LDL-induced inflammation, apoptosis and oxidative stress in HUVECs. PVT1 acted as a sponge of miR-153-3p, and GRB2 was confirmed as a target of miR-153-3p. MiR-153-3p overexpression attenuated the enhanced effects of PVT1 on ox-LDL-induced cell damage. GRB2 overexpression reversed the mitigating effects of miR-153-3p on ox-LDL-caused injury. Inhibiting PVT1 restrained the activation of ERK1/2 and p38 pathway via miR-153-3p/GRB2 axis. Additionally, silencing PVT1 in vivo reduced atherosclerotic plaques, lipid deposition, inflammation, oxidative stress, and apoptosis in AS mice.CONCLUSION:
PVT1 knockdown alleviated ox-LDL-induced vascular endothelial cell injury and atherosclerosis through miR-153-3p/GRB2 axis via ERK1/2 and p38 pathway.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
/
Aterosclerose
/
RNA Longo não Codificante
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nutr Metab Cardiovasc Dis
Assunto da revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
CIENCIAS DA NUTRICAO
/
METABOLISMO
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China