Abstract Fri006: Epigenetic Impacts of E-cigarette Nicotine Vaping and Implications for Heritable Abdominal Aortic Aneurysm Risk
Abstract
Background:
Smoking is the strongest modifiable risk factor for abdominal aortic aneurysm (AAA), but the risks of e-cigarette (e-cig) vaping are less well defined. Nicotine can cause heritable epigenetic alterations in animals and humans. We have found that nicotine infusion and e-cig vaping augment murine AAA, and that maternal e-cig vaping augments AAA in their offspring.
Hypothesis:
We investigated the effects of maternal e-cig vaping in mice on DNA methylation and accessibility in both parents and offspring, and evaluated effects of nicotine and e-cig condensate (ECC) on germ cells in culture.
Methods:
We treated female ApoE-/- and C57BL6J mice (F0) with e-cig nicotine vapor (24 mg/ml, 9 sec/min, 1 hour/day) or room air. Arm 1: mice were treated for 28 days, then mated to untreated controls. Arm 2: mice were mated after 1 week of e-cig exposure, then treated until end of gestation. In parallel mice, aortic tissue and blood were obtained for RRBS-Seq and ATAC-seq analysis to evaluate DNA methylation and accessibility after exposure. Offspring were aged to 10-12 weeks-old, and similarly assayed. We also evaluated abdominal aortic structure in offspring, and treated cultured spermatogonial stem cells and primary oocytes with nicotine or ECC.
Results:
Maternal e-cig exposure dramatically altered aortic DNA in both parents and offspring in both Arms, with numerous differentially methylated genes (DMGs). ATAC-seq identified hundreds of differentially accessible genes in their…
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