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Updated: Oct 1, 2025
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Published on: June 15, 2018
[MicroRNA-132 promotes atherosclerosis by inducing mitochondrial oxidative stressmediated ferroptosis]
1Dermatology Hospital of Southern Medical University, Guangzhou 510030, China.
Objective:
To explore the expression of microRNA-132 (miR-132) and its potential role in the development of atherosclerosis (AS).
Methods:
Thirty AS samples and 30 samples of normal peripheral vessels were collected from atherosclerotic patients undergoing peripheral angiostomy in our hospital for detecting the expression level of miR-132 using RT-qPCR. The expression of miR-132 in human umbilical vein endothelial cells (HUVEC) was up-regulated by liposome transfection, and intracellular reactive oxygen species (ROS), localization relationship between ROS and mitochondria, functional changes of mitochondrial reactive oxygen superoxide species (mtROS), mitochondrial membrane potential (MMP) and opening of mitochondrial permeability transition pore (mPTP) were analyzed by flow cytometry and laser confocal microscopy. The activity of mitochondrial redox respiratory chain complex (type I, II, III, IV and V) in HUVECs was detected using ELISA, and the expression levels of key iron death proteins were detected with Western blotting.
Results:
RT-qPCR results showed that miR-132 was significantly up-regulated in atherosclerotic plaques compared with normal vascular samples (P < 0.001). Compared with control HUVECs, HUVECs overexpressing miR-132 showed a significantly increased level of intracellular ROS (P < 0.001), and most of ROS was colocalized with mitochondria. HUVECs overexpressing miR-132 also showed significantly decreased MMP (P < 0.001) and obviously increased mtROS (P < 0.001) and opening of mPTP (P < 0.001), which led to mitochondrial REDOX respiratory chain stress disorder. The key iron death protein GPX4 was significantly down-regulated and the oxidized protein NOX4 was significantly increased in miR-132-overexpressing HUVECs (P < 0.001).
Conclusion:
MiR-132 promotes atherosclerosis by inducing mitochondrial oxidative stress-mediated ferroptosis, which may serve as a promising therapeutic target for AS.
Insights
MicroRNA-132 (miR-132) is elevated in atherosclerosis (AS) and promotes the disease by triggering mitochondrial oxidative stress and ferroptosis. This suggests miR-132 is a potential therapeutic target for AS.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Biochemistry
Background:
- Atherosclerosis (AS) is a chronic inflammatory disease characterized by plaque buildup in arteries.
- MicroRNAs (miRNAs) play crucial roles in regulating gene expression and are implicated in various diseases, including AS.
- Understanding the specific roles of miRNAs like miR-132 in AS pathogenesis is vital for developing targeted therapies.
Purpose of the Study:
- To investigate the expression levels of microRNA-132 (miR-132) in atherosclerosis.
- To elucidate the potential role of miR-132 in the development and progression of AS.
- To explore miR-132 as a potential therapeutic target for AS.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) was used to measure miR-132 expression in AS plaques and normal vascular samples.
- Human umbilical vein endothelial cells (HUVECs) were transfected to overexpress miR-132.
- Flow cytometry and laser confocal microscopy assessed intracellular reactive oxygen species (ROS), mitochondrial localization of ROS, mitochondrial reactive oxygen species (mtROS), mitochondrial membrane potential (MMP), and mitochondrial permeability transition pore (mPTP) opening.
- ELISA and Western blotting were employed to analyze mitochondrial respiratory chain complex activity and key ferroptosis-related proteins.
Main Results:
- miR-132 was significantly upregulated in atherosclerotic plaques compared to normal vessels (P < 0.001).
- Overexpression of miR-132 in HUVECs increased intracellular ROS, with significant colocalization in mitochondria, decreased MMP, and increased mtROS and mPTP opening.
- miR-132 overexpression led to mitochondrial redox respiratory chain dysfunction, downregulation of GPX4, and upregulation of NOX4, indicating ferroptosis induction.
Conclusions:
- MiR-132 promotes atherosclerosis by inducing mitochondrial oxidative stress-mediated ferroptosis.
- The findings highlight miR-132 as a key mediator in AS pathogenesis.
- MiR-132 represents a promising therapeutic target for the treatment of atherosclerosis.
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