An Overview of Adverse Outcome Pathway Links between PM_(2.5)Exposure and Cardiac Developmental Toxicity

作     者：Chen Liang Ruiyang Ding Qinglin Sun Shiqian Liu Zhiwei Sun Junchao Duan 

作者机构：Department of Toxicology and Sanitary ChemistrySchool of Public HealthCapital Medical UniversityBeijing 100069China Beijing Key Laboratory of Environmental ToxicologyCapital Medical UniversityBeijing 100069China 

出 版 物：《Environment & Health》 (环境与健康（英文）)

年 卷 期：2024年第2卷第3期

页      面：105-113页

学科分类：1002[医学-临床医学] 07[理学] 070602[理学-大气物理学与大气环境] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 0706[理学-大气科学] 10[医学] 

基　　金：supported by the National Key R&D Program of China(2022YFA0806900) 

主　　题：fine particulate matter adverse outcome pathways cardiac developmental toxicity congenital heart defects reactive oxygen species aryl hydrocarbon receptor 

摘      要：Fine particulate matter(PM_(2.5))is a significant risk factor for birth *** the first and most important organ to develop during embryogenesis,the heart’s potential susceptibility to PM_(2.5)has attracted growing *** several studies supporting the cardiac developmental toxicity of PM_(2.5),the diverse study types,models,and end points have prevented the integration of *** this Review,we present an adverse outcome pathway framework to elucidate the association between PM_(2.5)-induced molecular initiating events and adverse cardiac developmental *** of the aryl hydrocarbon receptor(AhR)and excessive generation of reactive oxygen species(ROS)were considered as molecular initiating *** excessive production of ROS induced oxidative stress,endoplasmic reticulum stress,DNA damage,and inflammation,resulting in *** activation of the AhR inhibited the Wnt/β-catenin pathway and then suppressed cardiomyocyte *** cardiomyocyte differentiation and persistent apoptosis resulted in abnormalities in the cardiac structure and *** of the aforementioned events have been identified as key events(KEs).The culmination of these KEs ultimately led to the adverse outcome,an increased morbidity of congenital heart defects(CHDs).This work contributes to understanding the causes of CHDs and promotes the safety evaluation of PM_(2.5).