Lysoglycerophospholipid metabolism alterations associated with ambient fine particulate matter exposure: Insights into the pro-atherosclerotic effects.

The biological pathways connecting ambient fine particulate matter (PM)-induced initial adverse effects to the development of atherosclerotic cardiovascular diseases are not fully understood. We hypothesize that lysoglycerophospholipids (LysoGPLs) are pivotal mediators of atherosclerosis induced by exposure to PM. This study investigated the changes of LysoGPLs in response to PM exposure and the mediation role of LysoGPLs in the pro-atherosclerotic effects of PM exposure. In this longitudinal panel study, 110 adults aged 50-65 years from Beijing, China, were followed between 2013 and 2015. Targeted metabolomics analyses were utilized to quantify 18 LysoGPLs from five subclasses in 579 plasma samples. Daily PM mass concentration was monitored at a station. We used linear mixed-effect models to estimate the responses of LysoGPLs to PM exposure. Subsequently, mediation analyses were conducted to investigate the mediating role of LysoGPLs in PM-associated changes in non-high density lipoprotein-cholesterol (Non-HDL-C), a biomarker for pro-atherosclerotic apolipoprotein B-containing lipoproteins, and various inflammatory biomarkers, including interleukin (IL)-8, monocyte chemoattractant protein-1 (MCP-1), soluble CD40 ligand, and interferon (IFN)-γ. Short-to medium-term (1-30 days) PM exposure was associated with significant increases in six lysophosphatidic acids (LPAs), three lysoalkylphosphatidylcholines [LPC(O)s], and three lysophosphatidylglycerols (LPGs), as well as decreases in two LPAs and one lysophosphatidylserine (LysoPS), with maximus changes of 0.5-2.1%, 0.8-2.1%, 1.9-3.0%, -1.4-3.7%, and -8.0%, respectively. Furthermore, the elevated levels of LPA 18:1/18:2, LPC(O) 18:0/18:1, and LPG 16:0/16:1/18:0 significantly mediated the PM-associated increase in Non-HDL-C (18-49%), IL-8 (9-24%), MCP-1 (12-26%), and IFN-γ (4-12%) over 30 days. In conclusion, short-to medium-term PM exposure was associated with altered metabolism of LysoGPLs, which mediated the PM-associated pro-atherosclerotic response.