Maternal E-cigarette Exposure Augments Murine Abdominal Aortic Aneurysm

Spin, J. M.; Mulorz, J. U.; Shen, W.-J.; Amirahmadi, M.; Rhee, Y. H.; Deng, A.; Chavan, S.; Butterfield, J.; Mulorz, P.; Wagenhauser, M. U.; Headley, C.; Qiu, T.; Tsao, P. S.

doi:10.64898/2026.10.19.760180

bioRxiv · 10.64898/2026.10.19.760180

Maternal E-cigarette Exposure Augments Murine Abdominal Aortic Aneurysm

Spin, J. M.·Mulorz, J. U.·Shen, W.-J.·Amirahmadi, M.·Rhee, Y. H.·Deng, A.·Chavan, S.·Butterfield, J.·Mulorz, P.·Wagenhauser, M. U.·Headley, C.·Qiu, T.·Tsao, P. S.

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Abstract

Background: Smoking and family history are major risk factors for abdominal aortic aneurysm (AAA). Smoking and nicotine are modulators of DNA methylation, capable of causing heritable epigenetic alterations. Nicotine infusion and e-cigarette (e-cig) vaping augment murine AAA. We investigated the effects of murine maternal e-cig vaping on offspring experimental AAA, and impacts on transgenerational DNA methylation and accessibility. Methods: We performed perinatal e-cig nicotine vaping in two strains of adult female mice (ApoE-/- and C57BL/6J). Mice were mated to control males, and treated through gestation. A parallel group were instead sacrificed after treatment, for DNA analysis. Offspring were aged to adulthood, and AAAs were then induced by elastase (C57BL/6J) or angiotensin-II infusion (ApoE-/-), and ultrasound-tracked for 4 weeks. In a second cohort, parental and offspring aortic tissue and blood DNA underwent RRBS and ATAC-seq analysis respectively. Offspring abdominal aortic anatomy was examined, and stiffness was assessed with ex vivo arterial myography. Results: Maternal e-cig exposure increased offspring AAA growth in both models and genders. AAA incidence was increased in ApoE-/- males, and observed effects were overall more pronounced in males. Maternal vape exposure altered aortic DNA methylation and blood DNA accessibility in mothers and offspring, with differential sites in numerous genes identified, including AAA-related genes and pathways. Pathways were enriched for transcription factors, inflammation/immune-related genes, and angiogenesis genes, with similar changes identified in exposed mothers. Male offspring displayed more differential genes. Significant changes were located in genes known to harbor AAA risk loci in humans, and overlapped with published epigenetic alterations in human smokers. Differences also occurred in offspring aortic structure and stiffness. Conclusions: Maternal e-cig nicotine exposure augments AAA growth in multiple models across generations. These effects are accompanied by broad epigenetic DNA reprogramming of key AAA modulator genes and pathways.

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Spin, J. M., Mulorz, J. U., Shen, W.-J., Amirahmadi, M., Rhee, Y. H., Deng, A., Chavan, S., Butterfield, J., Mulorz, P., Wagenhauser, M. U., Headley, C., Qiu, T., Tsao, P. S.. 2026-10-24. Maternal E-cigarette Exposure Augments Murine Abdominal Aortic Aneurysm. https://doi.org/10.64898/2026.10.19.760180

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