Screening Organic Components and Toxicogenic Structures from Regional Fine Particulate Matters Responsible for Myocardial Fibrosis in Male Mice.

Numerous studies indicate that fine particulate matters (PM 2.5 ) and its organic components are urgent risk factors for cardiovascular diseases (CVDs). Combining toxicological experiments, effect-directed analyses, and nontarget identification, this study aims to explore whether PM 2.5 exposure in coal-combustion areas induces myocardial fibrosis and how to identify the effective organic components and their toxic structures to support regional risk control. First, we constructed an animal model of real-world PM 2.5 exposure during the heating season and found that the exposure impaired cardiac systolic function and caused myocardial fibrosis, with chemokine Ccl2-mediated inflammatory response being the key cause of collagen deposition. Then, using the molecular event as target coupled with two-stage chromatographic isolation and mass spectrometry analyses, we identified a total of 171 suspect organic compounds in the PM 2.5 samples. Finally, using hierarchical characteristic fragment analysis, we predicted that 40 of them belonged to active compounds with 6 alert structures, including neopentane, butyldimethylamine, 4-ethylphenol, hexanal, decane, and dimethylaniline. These findings provide evidence for risk management and prevention of CVDs in polluted areas.