Biochemical Evidence of PM2.5 Critical Components in the Induction of Myocardial Fibrosis in Mice

Abstract Background:PM2.5 components are tightly linked to the initiation of a multitude of cardiovascular diseases (CVD). However, it is unclear that whether critical components of PM2.5 can induce myocardial fibrosis.Methods:We exposed female C57BL/6 mice to PM2.5 (3 mg/kg b.w.) from four different cities (Taiyuan, Beijing, Hangzhou, and Guangzhou) by oropharyngeal aspiration every other day. Thevarying degreesofmyocardial fibrosismarkers (Col1a1, Col3a1)and thepossible relevantindicators, including(E/E¢),NADPH oxidase 4 (NOX4), andtransforming growth factor β1 (TGFβ1)were detected by echocardiographyand / orqPCR and/ or Western blotinvivo.Pb, Cr, Mn, Zn, and most of thepolycyclic aromatic hydrocarbons (PAHs)were positive associated withdiastolic cardiac function andmyocardialfibrosisbyusingPearson correlation. BEAS-2b cells were treated with one or more of five candidate components with or without Guangzhou PM2.5, and the conditioned medium was used to culture AC16 cells. MTT assays were performed to evaluate the cytotoxicity of the treatments.ROS generation was detected by photocatalysis using 2¢,7¢-dichlorodihydrofluorescein diacetate (DCFHDA). The expression of Col1a1, TGFβ1 were detected by qPCRinvitro.Results:The effects of PM2.5 from Taiyuan are the most serious, while Guangzhou group caused minor effects. Zn + Pb + Mn + BaPwith PM2.5 from Guangzhou exposure significantly increased ROS production of BEAS-2b cells, and induced a dramatic increase of myocardial fiber-related gene expression (Col1a1 and TGF-β) in AC16 cells. Conclusion：It indicated that the different mass concentrations of Zn, Pb, Mn, and ΣPAHs in PM2.5mightbe the critical factor thatmodulated myocardial fibrosis induction by targeted. Our study provided anovel avenue for further elucidation of molecular mechanisms of PM2.5 components-induced myocardial fibrosis.