PM_2.5 and O₃ co-exposure affecting serum LDL-C: evidence from epidemiology and animal models

Air pollution and high low-density lipoprotein cholesterol (LDL-C) levels are both among the top ten global risk factors. This study aims to investigate the impact of long-term exposure to ambient PM2.5 and O3 on LDL-C concentrations in peripheral blood and their effects on hepatic metabolism of LDL-C, based on epidemiological research and animal experiments. Epidemiological research employed a cross-sectional design, enrolling 27,642 male health examinees aged 20-50 in Beijing from March 2021 to February 2023, with an exposure period of one year. Generalized additive models were employed to explore the association between exposure to PM2.5 and O3 and levels of LDL-C. The animal experiment involved rats exposed to an atmosphere containing PM2.5 and O3, alongside a control group breathing air devoid of PM2.5 and O3, with an exposure duration of 15 months. Reverse transcription quantitative polymerase chain reaction and immunohistochemical staining were utilized to detect differences in mRNA expression and protein expression at key loci of LDL-C metabolism between the two groups. In our results, the epidemiological research showed that long-term exposure to PM2.5 was primarily associated with increased levels of LDL-C and elevated risk of LDL-C abnormality. The animal experiments demonstrated that long-term exposure to air pollution suppressed the liver's ability to absorb LDL-C and inhibited the expression of GRP78, which may be one of the mechanisms leading to increased serum LDL-C levels.