Related Experiment Video
Updated: Nov 5, 2025
Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
MicroRNA-146a-3p/HDAC1/KLF5/IKBα signal axis modulates plaque formation of atherosclerosis mice
Huajin Liu1, Hongwei Wang1, Jiangwei Ma1
1Department of Cardiology, Fengxian District Central Hospital, Shanghai, China.
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.
Insights
MicroRNA-146a-3p (miR-146a-3p) depletion stabilizes atherosclerotic plaques by increasing histone deacetylase 1 (HDAC1) and inhibitors of kappa B alpha (IKBα) while decreasing Krüppel-like factor 5 (KLF5). This mechanism improves lipid profiles and reduces inflammation in atherosclerosis.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Immunology
Background:
- Atherosclerosis (AS) is an immune-inflammatory disease driven by lipids affecting medium and large arteries.
- Understanding the molecular mechanisms underlying AS plaque formation is crucial for developing effective treatments.
Purpose of the Study:
- To elucidate the role of the microRNA-146a-3p (miR-146a-3p)/histone deacetylase 1 (HDAC1)/Krüppel-like factor 5 (KLF5)/inhibitors of kappa B alpha (IKBα) signaling axis in AS plaque development.
- To investigate the therapeutic potential of targeting this axis in AS.
Main Methods:
- Established an AS mouse model using ApoE-/- mice on a high-fat diet for 12 weeks.
- Quantified expression of miR-146a-3p, KLF5, HDAC1, and IKBα in aortic tissues.
- Verified the direct targeting of HDAC1 by miR-146a-3p.
- Administered miR-146a-3p antagomir or HDAC1 overexpression in vivo and assessed effects on blood lipids, inflammatory factors, apoptosis, and plaque area.
- Evaluated vascular endothelial cell (VEC) proliferation and apoptosis in vitro.
Main Results:
- AS mice exhibited increased miR-146a-3p and KLF5, with decreased HDAC1 and IKBα in aortic tissues.
- miR-146a-3p was confirmed to directly target HDAC1.
- miR-146a-3p depletion or HDAC1 restoration lowered plasma lipids, reduced serum inflammatory factors, attenuated aortic apoptosis, enhanced antioxidant capacity, and improved plaque stability.
- Downregulation of miR-146a-3p or upregulation of HDAC1 promoted VEC proliferation and inhibited apoptosis.
Conclusions:
- Functional studies demonstrate that reduced miR-146a-3p enhances HDAC1 and IKBα expression while suppressing KLF5.
- This modulation facilitates pathological plaque stability in atherosclerosis mouse models.
- The miR-146a-3p/HDAC1/KLF5/IKBα axis represents a potential therapeutic target for AS.
