Zhao Yixue, Shen Geng, Lin Xipeng, Zhang Long, Fan Fangfang, Zhang Yan, Li Jianping
Division of Cardiology, Peking University First Hospital, Beijing 100034, China.
Institute of Cardiovascular Disease, Peking University First Hospital, Beijing 100034, China.
Toxics. 2023 Sep 29;11(10):823. doi: 10.3390/toxics11100823.
Air pollution is an important public health problem that endangers human health. However, the casual association and pathogenesis between particles < 2.5 μm (PM) and hyperlipidemia remains incompletely unknown. Mendelian randomization (MR) and transcriptomic data analysis were performed, and an air pollution model using mice was constructed to investigate the association between PM and hyperlipidemia. MR analysis demonstrated that PM is associated with hyperlipidemia and the triglyceride (TG) level in the European population (IVW method of hyperlipidemia: OR: 1.0063, 95%CI: 1.0010-1.0118, = 0.0210; IVW method of TG level: OR: 1.1004, 95%CI: 1.0067-1.2028, = 0.0350). Mest, Adipoq, Ccl2, and Pcsk9 emerged in the differentially expressed genes of the liver and plasma of PM model mice, which might mediate atherosclerosis accelerated by PM. The studied animal model shows that the Paigen Diet (PD)-fed male LDLR mice had higher total cholesterol (TC), TG, and CM/VLDL cholesterol levels than the control group did after 10 times 5 mg/kg PM intranasal instillation once every three days. Our study revealed that PM had causality with hyperlipidemia, and PM might affect liver secretion, which could further regulate atherosclerosis. The lipid profile of PD-fed Familial Hypercholesterolemia (FH) model mice is more likely to be jeopardized by PM exposure.
空气污染是一个危及人类健康的重要公共卫生问题。然而，直径小于2.5微米的颗粒物（PM）与高脂血症之间的因果关系及发病机制仍不完全清楚。我们进行了孟德尔随机化（MR）和转录组数据分析，并构建了一个使用小鼠的空气污染模型来研究PM与高脂血症之间的关联。MR分析表明，在欧洲人群中，PM与高脂血症及甘油三酯（TG）水平相关（高脂血症的逆方差加权法：比值比：1.0063，95%置信区间：1.0010 - 1.0118，P = 0.0210；TG水平的逆方差加权法：比值比：1.1004，95%置信区间：1.0067 - 1.2028，P = 0.0350）。Mest、Adipoq、Ccl2和Pcsk9出现在PM模型小鼠肝脏和血浆的差异表达基因中，它们可能介导了由PM加速的动脉粥样硬化。所研究的动物模型显示，在每隔三天一次、每次5毫克/千克PM经鼻滴注10次后，食用派根饮食（PD）的雄性低密度脂蛋白受体（LDLR）小鼠的总胆固醇（TC）、TG和CM/VLDL胆固醇水平高于对照组。我们的研究表明，PM与高脂血症存在因果关系，并且PM可能影响肝脏分泌，进而进一步调节动脉粥样硬化。食用PD的家族性高胆固醇血症（FH）模型小鼠的血脂谱更有可能因暴露于PM而受到损害。
