The mitochondria-targeted antioxidant MitoQ attenuated PM(2.5)-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 Ca(2+), 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.