Chronic Real-Ambient PM_(2.5)Exposure Exacerbates Cardiovascular Risk via Amplifying Liver Injury in Mice Fed with a High-Fat and High-Cholesterol Diet  

作　　者：Yi Chen Hiu Lok Ngan Yuanyuan Song Zenghua Qi Lifang Zhao Chuan Dong Ruijin Li Yanbo Li Zhu Yang Zongwei Cai 

机构地区：[1]State Key Laboratory of Environmental and Biological Analysis,Department of Chemistry,Hong Kong Baptist University,Hong Kong SAR 000000,China [2]School of Environmental Science and Engineering,Guangdong University of Technology,Guangzhou 510006,China [3]Institute of Environmental Science,Shanxi University,Taiyuan 030006,China [4]Beijing Key Laboratory of Environmental Toxicology,Capital Medical University,Beijing 100029,China

出　　处：《Environment & Health》2024年第4期221-232,共12页环境与健康（英文）

基　　金：supported by National Key Research and Development Program of China(2018YFA0901104);National Natural Science Foundation of China(91843301);Hong Kong General Research Fund(12302922,12303320,and 12103820);internal research funds SKLP_2223_P04 from Hong Kong Baptist University.

摘　　要：Epidemiology has associated fine particulate matter(PM_(2.5))exposure with an increased cardiovascular risk.However,the underlying mechanism,particularly from the liver perspective,remains unclear.Here,the influence of chronic PM_(2.5)exposure on cardiovascular risk in mice fed a high-fat and high-cholesterol diet(HFCD)was studied by using a real-world PM_(2.5)exposure system.Results showed that PM_(2.5)exposure elevated the serum levels of nonhigh-density lipoprotein cholesterol(non-HDL-C)and oxidized low-density lipoprotein(oxLDL)in HFCD-fed mice,demonstrating increased cardiovascular risk.To investigate the molecular mechanism,lipidomics and metabolomics analyses were conducted and revealed that PM_(2.5)exposure enhanced lipid accumulation and disturbed purine metabolism and glutathione metabolism in the liver of HFCD-fed mice,contributing to the elevated non-HDL-C levels and intensified oxidative stress.Moreover,PM_(2.5)exposure increased total cholesterol levels by upregulating Hmgcr expression and downregulating Cyp7a1 expression in the livers of HFCD-fed mice.The HDL-C level was reduced by inhibiting the hepatic Abca1 and Abcg1 expression and decreasing the levels of ApoA-I and LCAT.Additionally,the PM_(2.5)-induced pro-oxidative environment impeded the oxLDL clearance and further triggered inflammation,in turn exacerbating oxidative stress and oxLDL production.This study demonstrated a synergy of PM_(2.5)and HFCD on cardiovascular risk and illuminated the molecular mechanism in PM_(2.5)-susceptible populations.

关 键 词：PM_(2.5) HFCD Metabolomics LIPIDOMICS Cardiovascular risk 

分 类 号：R54[医药卫生—心血管疾病]