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

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

  • Redox Biol. 2021 Oct;46:102113. doi: 10.1016/j.redox.2021.102113.
Ruihong Ning 1,  Yang Li 1,  Zhou Du 1,  Tianyu Li 1,  Qinglin Sun 1,  Lisen Lin 1,  Qing Xu 2,  Junchao Duan 3,  Zhiwei Sun 4
Affiliations

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.
PMID: 34425389 DOI: 10.1016/j.redox.2021.102113
Abstract

Short-term PM2.5 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 PM2.5. Therefore, the current study was aimed to evaluate the protective role of MitoQ on aortic fibrosis induced by PM2.5 exposure. Vascular Doppler ultrasound manifested PM2.5 damaged both vascular function and structure in C57BL/6J mice. Histopathological analysis found that PM2.5 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 PM2.5-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 PM2.5-exposed aorta and HAVSMCs were weakened by MitoQ. Transfection with PINK1 siRNA in PM2.5-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 PM2.5 exposure through mitochondrial quality control, which regulated by mitochondrial ROS/PINK1/Parkin-mediated Mitophagy. Our study provides a possible targeted therapy for PM2.5-induced arterial stiffness.

Keywords

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

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