Abstract 4747: Chronic E-cigarette aerosol exposure induces metabolic, translational, and immune reprogramming in mice: A serum proteomics analysis

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Abstract Background: E-cigarette aerosol exposure has been associated with inflammation and oxidative stress; however, its systemic metabolic effects remain poorly understood. Because circulating serum proteins capture early physiological perturbations, we examined how chronic e-cigarette exposure alters metabolic, translational, and immune pathways using a controlled mouse model. Methods: We subjected C57BL/6 mice to chronic exposure to e-cigarette aerosols for 10 weeks, with filtered-air controls. Serum samples were collected and analyzed through untargeted LC-MS/MS proteomics. Gene Set Enrichment Analysis (GSEA) was performed using GO, KEGG, Hallmark, and MSigDB immune signatures to identify pathway-level alterations in metabolism, redox biology, translational control, and immune signaling. Results: Our findings reveal that chronic exposure to e-cigarette aerosols triggers metabolic reprogramming, marked by significant enrichment of pathways related to oxidative phosphorylation, fatty acid metabolism, pyruvate metabolism, vesicle trafficking, and detoxification of reactive oxygen species (ROS). We observed increased levels of redox-adaptive and glycolytic proteins (PKM, IDH1/2, NQO1, GSTM1/2, GSS), indicating a shift toward NADPH-driven antioxidant metabolism and mitochondrial remodeling, consistent with systemic metabolic stress. This metabolic shift was accompanied by strong translational reprogramming, including enrichment of ribonucleoprotein complex assembly and mRNA processing pathways. Increased expression of translation-associated factors, such as eIF4A2, further supported activation of an stress-responsive translational program. Immune analyses revealed selective enrichment of natural killer (NK) cell-associated pathways, indicating altered NK cell functional signatures following chronic e-cigarette exposure. This targeted shift in innate immunity is consistent with the observed metabolic and translational remodeling, as NK cell activity relies heavily on glycolytic and stress-adaptive translational programs. Conclusion: Chronic e-cigarette exposure leads to interconnected changes in metabolic, translational, and immune processes in mice. The resultant shifts towards antioxidant and glycolytic pathways, stress-responsive translation, and altered immune signaling suggest that metabolic-immune crosstalk serves as an early systemic mechanism of vaping toxicity, warranting targeted validation through metabolic, translational, and immune profiling. Citation Format: Rizwana Begum, Ganesan Muthusamy, Shreya Pokharel, Biplov Sapkota, Poorna Sai Vaddi, Shang SU, Abhishek Pandit, Naveen Chintala Ramulu, Joseph Francis. Chronic E-cigarette aerosol exposure induces metabolic, translational, and immune reprogramming in mice: A serum proteomics analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4747.

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