ESC Congress 2026 Abstract · Oct 26, 2026
Mechanisms underlying ApoC3-mediated PM2.5-Induced atherosclerotic cardiovascular disease
By Zhao Y, Li J
Objective: Air pollution, particularly fine particulate matter (PM2.5), is a major global public health concern and key cardiovascular risk factor. Although PM2.5 is linked to coronary artery disease, its role in promoting atherosclerosis via lipid metabolism dysregulation and plaque destabilization remains unclear. This study aimed to elucidate the mechanisms by which PM2.5 accelerates atherosclerosis progression and adverse outcomes using molecular, genetic, and epidemiological approaches. Methods: A multi-dimensional strategy integrating multi-omics analyses, animal and cellular models, genetic causal inference, and population-based investigations was applied. Single-cell RNA sequencing was performed in PM2.5- and high-fat diet–exposed atherosclerosis mice to characterize vascular cellular changes and intercellular communication. ApoC3 overexpression and knockout mouse models were constructed to assess plaque burden and stability. Exosomal proteomics and cell co-culture systems verified interorgan signaling. In vitro macrophage models examined the effects of ApoC3 on apoptosis, efferocytosis, and inflammation. A real-world cohort of patients with acute myocardial infarction (AMI) was analyzed using multivariable Cox regression to evaluate associations between air pollutant exposure and AMI-related mortality. Results: (1) Single-cell analysis showed that PM2.5 enhanced monocyte and macrophage recruitment and altered MerTK signaling. (2) Mechanistically, PM2.5 induced bronchial epithelial cells to release exosomes carrying AKR1B1, which entered hepatocytes and upregulated ApoC3 expression, aggravating lipid metabolic disorders. ApoC3 overexpression promoted plaque formation, whereas ApoC3 deficiency improved plaque stability. ApoC3 knockdown enhanced macrophage efferocytosis by reducing CBL-mediated MerTK ubiquitination. (3) In the population study, exposure to PM2.5, PM10, NO₂, and O₃ was higher in AMI non-survivors, and PM2.5 remained independently associated with increased AMI-related mortality. Conclusion: PM2.5 induces lipid metabolic disorders via the exosomal AKR1B1–ApoC3 axis and accelerates atherosclerosis and plaque destabilization by impairing MerTK-mediated efferocytosis, thereby increasing mortality risk in patients with AMI. This study provides mechanistic and epidemiological evidence linking PM2.5 to atherosclerotic cardiovascular disease and identifies ApoC3 and efferocytosis as potential therapeutic targets.GA