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

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.