Concurrent chronic-plus-binge alcohol and nicotine vaping alter cardiac ventricular proteome in a preclinical model

Nicotine vaping has surged in recent years, particularly among young adults, and is strongly linked with concurrent alcohol use. Separately, chronic plus binge alcohol use drives hypertension and cardiomyopathy, while nicotine vaping is linked to a modest rise in cardiovascular disease incidence and mortality. However, little is known about how concurrent use interacts to affect the cardiovascular system. The aim of this study was to determine differential cardiac protein expression in mice exposed to concurrent chronic plus binge alcohol and nicotine vaping use. Male C57BL6/J mice received a 20-day 5% ethanol diet with 5 g/kg ethanol binges on days 10 and 20, alongside isocaloric controls. During this period, they were also exposed nightly to either 5% nicotine salt vapor, vegetable glycerin/propylene glycol vehicle vapor, or room air. The left ventricular free wall was collected and analyzed using discovery-based proteomics and subsequent Ingenuity Pathway Analysis. 2708 proteins were uniformly expressed across all groups. Compared to air-exposed, control-fed mice, 201 proteins were significantly altered by ethanol, 101 proteins by nicotine vaping, and 159 proteins by combined exposure. Both ethanol and nicotine vaping influenced pathways involved in lipid homeostasis, calcium handling, and mitochondrial bioenergetics; however, these alterations did not uniformly manifest in the dual-use group. This pattern underscores the nonadditive and potentially interaction-dependent nature of alcohol and nicotine vaping effects on cardiovascular biology Funding: F30AA031632 (NH), 24PRE1201394- AHA (NH), F30AA030910 (EG), R21AA029747 (JG) This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.