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

Haonan Li; Yiqun Han; Wu Chen; Yanwen Wang; Yifan Xu; Teng Wang; Jicheng Gong; Weiju Li; Hongyin Zhang; Junxia Wang; Xinghua Qiu; Tong Zhu

doi:10.1016/j.envpol.2025.125646

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

Environ Pollut. 2025 Jan 4:125646. doi: 10.1016/j.envpol.2025.125646. Online ahead of print.

Authors

Haonan Li¹, Yiqun Han², Wu Chen³, Yanwen Wang⁴, Yifan Xu¹, Teng Wang⁵, Jicheng Gong¹, Weiju Li⁶, Hongyin Zhang⁶, Junxia Wang¹, Xinghua Qiu¹, Tong Zhu⁷

Affiliations

¹ SKL-ESPC & SEPKL-AERM, College of Environmental Sciences and Engineering, and Center for Environment and Health, Peking University, Beijing, China.
² SKL-ESPC & SEPKL-AERM, College of Environmental Sciences and Engineering, and Center for Environment and Health, Peking University, Beijing, China; Environmental Research Group, MRC Centre for Environment and Health, Imperial College London, London, UK.
³ SKL-ESPC & SEPKL-AERM, College of Environmental Sciences and Engineering, and Center for Environment and Health, Peking University, Beijing, China; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, USA.
⁴ SKL-ESPC & SEPKL-AERM, College of Environmental Sciences and Engineering, and Center for Environment and Health, Peking University, Beijing, China; National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, China.
⁵ SKL-ESPC & SEPKL-AERM, College of Environmental Sciences and Engineering, and Center for Environment and Health, Peking University, Beijing, China; School of Health Policy and Management, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
⁶ Peking University Hospital, Peking University, Beijing, China.
⁷ SKL-ESPC & SEPKL-AERM, College of Environmental Sciences and Engineering, and Center for Environment and Health, Peking University, Beijing, China. Electronic address: [email protected].

PMID: 39761719
DOI: 10.1016/j.envpol.2025.125646

Abstract

The biological pathways connecting ambient fine particulate matter (PM_2.5)-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_2.5. This study investigated the changes of LysoGPLs in response to PM_2.5 exposure and the mediation role of LysoGPLs in the pro-atherosclerotic effects of PM_2.5 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_2.5 mass concentration was monitored at a station. We used linear mixed-effect models to estimate the responses of LysoGPLs to PM_2.5 exposure. Subsequently, mediation analyses were conducted to investigate the mediating role of LysoGPLs in PM_2.5-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_2.5 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_2.5-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_2.5 exposure was associated with altered metabolism of LysoGPLs, which mediated the PM_2.5-associated pro-atherosclerotic response.

Keywords: Air pollution; atherosclerosis; lipidomics; lysophospholipid; metabolomics.