Mitochondrial dysfunction drives persistent vascular fibrosis in rats after short-term exposure of PM2.5.

Nowadays, the great majority of toxicological studies have focused on immediate cardiovascular effects of simultaneous exposure to long-term or short-term PM2.5; yet, whether the persistent vascular fibrosis will be induced after short-term PM2.5 exposure and its related underlying mechanisms remain unclear. In this study, we adopted SD rats treated with PM2.5 for 1 month and followed by 12 months and 18 months recovery. Results from Doppler ultrasonography and histopathological analysis found that PM2.5-evoked vascular fibrosis was comprised of structural injury, including thickening of aortic media and carotid intima media thickness (CIMT), narrow left common carotid artery (LCCA), collagen deposition, impaired elasticity and functional alterations in aortal stiffness during long-term recovery. The protein expression levels of collagen I, collagen III, proliferating cell nuclear antigen (PNCA), TGF-β and osteopontin (OPN) remained elevated trends in PM2.5-treated groups for the related period than in control groups. Additionally, PM2.5 upregulated the protein expression levels of superoxide dismutase 2 (SOD2), mitochondrial fission related proteins (Drp1 and Fis1), while downregulated the protein expression levels of mitochondrial fusion related proteins (Mfn2 and OPA1). Moreover, PM2.5 significantly activated the mitophagy-related protein expression, including LC3, p62, PINK, Parkin. In summary, our results demonstrated that short-term PM2.5 exposure could trigger mitophagy, further lead to mitochondrial dysfunction which regulated persistent vascular fibrosis during long-term recovery.