Identifying the Relationship between PM(2.5) and Hyperlipidemia Using Mendelian Randomization, RNA-seq Data and Model Mice Subjected to Air Pollution

Air pollution is an important public health problem that endangers human health. However, the casual association and pathogenesis between particles < 2.5 μm (PM(2.5)) 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(2.5) and hyperlipidemia. MR analysis demonstrated that PM(2.5) 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, p = 0.0210; IVW method of TG level: OR: 1.1004, 95%CI: 1.0067–1.2028, p = 0.0350). Mest, Adipoq, Ccl2, and Pcsk9 emerged in the differentially expressed genes of the liver and plasma of PM(2.5) model mice, which might mediate atherosclerosis accelerated by PM(2.5). 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(2.5) intranasal instillation once every three days. Our study revealed that PM(2.5) had causality with hyperlipidemia, and PM(2.5) 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(2.5) exposure.