The mitochondria-targeted antioxidant MitoQ attenuated PM2.5-induced vascular fibrosis via regulating mitophagy

Ruihong Ning; Yang Li; Zhou Du; Tianyu Li; Qinglin Sun; Lisen Lin; Qing Xu; Junchao Duan; Zhiwei Sun

doi:10.1016/j.redox.2021.102113

The mitochondria-targeted antioxidant MitoQ attenuated PM_2.5-induced vascular fibrosis via regulating mitophagy

Redox Biol. 2021 Oct:46:102113. doi: 10.1016/j.redox.2021.102113. Epub 2021 Aug 18.

Authors

Ruihong Ning¹, Yang Li¹, Zhou Du¹, Tianyu Li¹, Qinglin Sun¹, Lisen Lin¹, Qing Xu², Junchao Duan³, Zhiwei Sun⁴

Affiliations

¹ Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, PR China.
² Core Facilities Center, Capital Medical University, Beijing, 100069, People's Republic of China.
³ Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, PR China. Electronic address: jcduan@ccmu.edu.cn.
⁴ Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, PR China. Electronic address: zwsun@ccmu.edu.cn.

Abstract

Short-term PM_2.5 exposure is related to vascular remodeling and stiffness. Mitochondria-targeted antioxidant MitoQ is reported to improve the occurrence and development of mitochondrial redox-related diseases. At present, there is limited data on whether MitoQ can alleviate the vascular damage caused by PM_2.5. Therefore, the current study was aimed to evaluate the protective role of MitoQ on aortic fibrosis induced by PM_2.5 exposure. Vascular Doppler ultrasound manifested PM_2.5 damaged both vascular function and structure in C57BL/6J mice. Histopathological analysis found that PM_2.5 induced aortic fibrosis and disordered elastic fibers, accompanied by collagen I/III deposition and synthetic phenotype remodeling of vascular smooth muscle cells; while these alterations were partially alleviated following MitoQ treatment. We further demonstrated that mitochondrial dysfunction, including mitochondrial reactive oxygen species (ROS) overproduction and activated superoxide dismutase 2 (SOD2) expression, decreased mitochondrial membrane potential (MMP), oxygen consumption rate (OCR), ATP and increased intracellular Ca²⁺, as well as mitochondrial fragmentation caused by increased Drp1 expression and decreased Mfn2 expression, occurred in PM_2.5-exposed aorta or human aortic vascular smooth muscle cells (HAVSMCs), which were reversed by MitoQ. Moreover, the enhanced expressions of LC3II/I, p62, PINK1 and Parkin regulated mitophagy in PM_2.5-exposed aorta and HAVSMCs were weakened by MitoQ. Transfection with PINK1 siRNA in PM_2.5-exposed HAVSMCs further improved the effects of MitoQ on HAVSMCs synthetic phenotype remodeling, mitochondrial fragmentation and mitophagy. In summary, our data demonstrated that MitoQ treatment had a protective role in aortic fibrosis after PM_2.5 exposure through mitochondrial quality control, which regulated by mitochondrial ROS/PINK1/Parkin-mediated mitophagy. Our study provides a possible targeted therapy for PM_2.5-induced arterial stiffness.

Keywords: MitoQ; Mitochondrial dysfunction; Mitophagy; Short-term PM(2.5) exposure; Vascular fibrosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antioxidants*
Fibrosis
Mice
Mice, Inbred C57BL
Mitochondria
Mitophagy*
Particulate Matter / toxicity
Reactive Oxygen Species

Substances

Antioxidants
Particulate Matter
Reactive Oxygen Species