MicroRNA-146a-3p/HDAC1/KLF5/IKBα signal axis modulates plaque formation of atherosclerosis mice.

Abstract

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:

ApoE-/- mice were fed with high-fat feed for 12 weeks to establish AS mice model. The expression of miR-146a-3p, KLF5, HDAC1 and IKBα in aortic wall tissues of AS mice was tested. The targeting relationship between miR-146a-3p and HDAC1 was verified. AS mice were injected with miR-146a-3p antagomir or HDAC1 overexpression to verify the impacts of miR-146a-3p and HDAC1 on blood lipids and inflammatory factors in serum, aortic wall apoptotic cells, antioxidant stress capacity and the plaque area in AS mice. VECs proliferation and apoptosis were also measured in vitro.

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:

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.

• Authors: Huajin Liu, Hongwei Wang, Jiangwei Ma, Zengyong Qiao, Li Zhang, Guanghao Ge
• Journal: Life sciences (Life Sci) Vol. 284 Pg. 119615 (Nov 01 2021) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 34004248 (Publication Type: Journal Article)
• Copyright: Copyright © 2021. Published by Elsevier Inc.

Chemical References

• Antioxidants
• Klf5 protein, mouse
• Kruppel-Like Transcription Factors
• Lipids
• MicroRNAs
• Mirn146 microRNA, mouse
• NF-KappaB Inhibitor alpha
• Histone Deacetylase 1

Topics

• Animals
• Antioxidants (metabolism)
• Apoptosis (genetics)
• Atherosclerosis (blood, genetics, pathology)
• Base Sequence
• Cell Proliferation (genetics)
• Down-Regulation (genetics)
• Endothelial Cells (metabolism, pathology)
• Histone Deacetylase 1 (genetics, metabolism)
• Inflammation (blood, pathology)
• Kruppel-Like Transcription Factors (genetics, metabolism)
• Lipids (blood)
• Male
• Mice, Inbred C57BL
• MicroRNAs (genetics, metabolism)
• NF-KappaB Inhibitor alpha (metabolism)
• Plaque, Atherosclerotic (blood, genetics)
• Signal Transduction (genetics)
• Up-Regulation (genetics)
• Mice