Identifying the Relationship between PM_2.5 and Hyperlipidemia Using Mendelian Randomization, RNA-seq Data and Model...

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.