MicroRNA-146a-3p/HDAC1/KLF5/IKBα signal axis modulates plaque formation of atherosclerosis mice.
Animals
Antioxidants
/ metabolism
Apoptosis
/ genetics
Atherosclerosis
/ blood
Base Sequence
Cell Proliferation
/ genetics
Down-Regulation
/ genetics
Endothelial Cells
/ metabolism
Histone Deacetylase 1
/ genetics
Inflammation
/ blood
Kruppel-Like Transcription Factors
/ genetics
Lipids
/ blood
Male
Mice, Inbred C57BL
MicroRNAs
/ genetics
NF-KappaB Inhibitor alpha
/ metabolism
Plaque, Atherosclerotic
/ blood
Signal Transduction
/ genetics
Up-Regulation
/ genetics
Atherosclerosis
Histone deacetylase 1
Inhibitors of kappa B α
Krüppel-like factor 5
MicroRNA-146a-3p
Plaque area
Journal
Life sciences
ISSN: 1879-0631
Titre abrégé: Life Sci
Pays: Netherlands
ID NLM: 0375521
Informations de publication
Date de publication:
01 Nov 2021
01 Nov 2021
Historique:
received:
06
09
2020
revised:
06
05
2021
accepted:
07
05
2021
pubmed:
19
5
2021
medline:
8
10
2021
entrez:
18
5
2021
Statut:
ppublish
Résumé
Atherosclerosis (AS) is a multifocal, smoldering immune inflammatory disease of medium and large arteries driven by lipids. The aim of this study is to discuss the mechanism of microRNA-146a-3p (miR-146a-3p)/histone deacetylase 1 (HDAC1)/Krüppel-like factor 5 (KLF5)/inhibitors of kappa B α (IKBα) signal axis in plaque formation of AS mice. ApoE miR-146a-3p and KLF5 were increased while HDAC1 and IKBα were reduced in aortic wall tissues of AS mice. miR-146a-3p directly targeted to HDAC1. Depletion of miR-146a-3p or restoration of HDAC1 was correlated to lower plasma lipid level, reduced inflammatory factors in serum, attenuated aortic wall apoptosis, increased antioxidant stress capacity and improved the stability of pathological plaque of AS mice. miR-146a-3p down-regulation or HDAC1 up-regulation promoted VECs proliferation and inhibited apoptosis. Functional studies show that depleted miR-146a-3p advances HDAC1 and IKBα expression as well as inhibits KLF5 expression to facilitate the stability of pathological plaques in AS mice.
Sections du résumé
BACKGROUND
BACKGROUND
Atherosclerosis (AS) is a multifocal, smoldering immune inflammatory disease of medium and large arteries driven by lipids. The aim of this study is to discuss the mechanism of microRNA-146a-3p (miR-146a-3p)/histone deacetylase 1 (HDAC1)/Krüppel-like factor 5 (KLF5)/inhibitors of kappa B α (IKBα) signal axis in plaque formation of AS mice.
METHODS
METHODS
ApoE
RESULTS
RESULTS
miR-146a-3p and KLF5 were increased while HDAC1 and IKBα were reduced in aortic wall tissues of AS mice. miR-146a-3p directly targeted to HDAC1. Depletion of miR-146a-3p or restoration of HDAC1 was correlated to lower plasma lipid level, reduced inflammatory factors in serum, attenuated aortic wall apoptosis, increased antioxidant stress capacity and improved the stability of pathological plaque of AS mice. miR-146a-3p down-regulation or HDAC1 up-regulation promoted VECs proliferation and inhibited apoptosis.
CONCLUSION
CONCLUSIONS
Functional studies show that depleted miR-146a-3p advances HDAC1 and IKBα expression as well as inhibits KLF5 expression to facilitate the stability of pathological plaques in AS mice.
Identifiants
pubmed: 34004248
pii: S0024-3205(21)00601-9
doi: 10.1016/j.lfs.2021.119615
pii:
doi:
Substances chimiques
Antioxidants
0
Klf5 protein, mouse
0
Kruppel-Like Transcription Factors
0
Lipids
0
MicroRNAs
0
Mirn146 microRNA, mouse
0
NF-KappaB Inhibitor alpha
139874-52-5
Histone Deacetylase 1
EC 3.5.1.98
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
119615Informations de copyright
Copyright © 2021. Published by Elsevier Inc.