Relationships of Liver X Receptor Antagonists and Atherosclerosis in Drinking Water from Six Chinese Major Cities.
Xinming ShenQiang LiWenxin HuMin YangWei AnJianying HuPublished in: Environmental science & technology (2023)
While environmental factors have been considered contributors to atherosclerosis, it remains unclear whether drinking water promotes foam cell formation, the initial event of atherosclerosis. This study revealed that drinking water from six major cities in China, namely, Harbin, Jinan, Shanghai, Wuhan, Chongqing, and Zhuhai, significantly promoted foam cell formation in an in vitro macrophage model at a minimum concentration fold of 2. Moreover, cholesterol efflux was significantly impeded by all samples at 2-16-fold, while cholesterol influx was induced only by samples from Jinan and Chongqing at 16-fold, suggesting the dominant role of efflux in foam cell formation. Interestingly, except for the sample from Jinan, the samples exhibited complete inhibition of liver X receptor α (LXRα) activities at 160-fold, indicating the potential role of chemicals in drinking water in promoting foam cell formation by antagonizing LXRα. Through LXRα protein affinity selection-mass spectrometry, we identified ten LXRα-binding compounds, with efavirenz being revealed for the first time as a significant inducer of foam cell formation through LXRα antagonism. Overall, this study clarifies the atherosclerotic risks posed by drinking water and demonstrates the efavirenz-related atherosclerotic effects.
Keyphrases
- drinking water
- single cell
- health risk assessment
- health risk
- cell therapy
- mass spectrometry
- stem cells
- climate change
- oxidative stress
- high resolution
- antiretroviral therapy
- heavy metals
- coronavirus disease
- liquid chromatography
- mesenchymal stem cells
- ms ms
- risk assessment
- human health
- low density lipoprotein
- transcription factor
- high performance liquid chromatography
- stress induced
- tandem mass spectrometry