MicroRNA-132 promotes atherosclerosis by inducing mitochondrial oxidative stressmediated ferroptosis.
10.12122/j.issn.1673-4254.2022.01.18
- Author:
Ze Xin LIU
1
;
Sai CAO
2
;
Qing CHEN
3
;
Fang Yong FU
4
;
Mei Rong CHENG
5
;
Xian Ying HUANG
4
Author Information
1. Dermatology Hospital of Southern Medical University, Guangzhou 510030, China.
2. Department of Thoracic Surgery, Southern Medical University, Guangzhou 510515, China.
3. Department of Vascular Surgery, Third Affiliated Hospital of Southern Medical University, Guangzhou 510665, China.
4. Department of Vascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
5. Zengcheng Branch of Nanfang Hospital, Southern Medical University, Guangzhou 511300, China.
- Publication Type:Journal Article
- Keywords:
atherosclerosis;
ferroptosis;
microRNA-132;
oxidative stress
- MeSH:
Apoptosis;
Atherosclerosis/genetics*;
Ferroptosis;
Human Umbilical Vein Endothelial Cells/metabolism*;
Humans;
Membrane Potential, Mitochondrial;
MicroRNAs/metabolism*;
Mitochondria/metabolism*;
Oxidation-Reduction;
Oxidative Stress;
Reactive Oxygen Species/metabolism*
- From:
Journal of Southern Medical University
2022;42(1):143-149
- CountryChina
- Language:Chinese
-
Abstract:
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.
