313 - Autophagy Activation as a Potential Approach to Mitigate Pulmonary Risks from Maternal E-Cigarette Use

Publication Number: 313.4008

Noushin Lotfi, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, United States; Ying Wang, The Lundquist Institute, Torrance, CA, United States; Gourav Chandan, Lundquist Institute, Torrance, CA, United States; Sabrina Madrigal, The Lundquist Institute, Monterey Park, CA, United States; Harvey Perez, The Lundquist Institute, Lakewood, CA, United States; Omid Akbari, USC Keck school of Medicine, Los Angeles, CA, United States; Virender K. Rehan, Harbor-UCLA Medical Center, Torrance, CA, United States

Background: Maternal autophagy, essential for maintaining cellular homeostasis, significantly influences the immune development of offspring, especially concerning respiratory health. Autophagy disruption in mothers can cause asthma and inflammation in offspring. While vaping is becoming more popular as a "safer" alternative to smoking, its effects on maternal lung autophagy and offspring health remain unknown.

Objective: We hypothesize that e-cigarettes suppress maternal lung autophagy, increasing offspring susceptibility to asthma and infections. We examine the effects of nicotine vaping on lung autophagy in young adult female mice to test this hypothesis.

Design/Methods: We exposed eight-week-old C57BL/6J female mice twice daily for 2 hours over 6 weeks to either filtered air (Control), PG/VG with 4.8% nicotine, or PG/VG without 4.8% nicotine. We collected lung tissues and bronchoalveolar lavage (BAL). Autophagy markers (LC3B, p62), inflammatory cytokines (IL-1β, IL-6, GM-CSF, MCP-1), and markers of mesenchymal differentiation and injury repair (CTGF, fibronectin, collagen III, vimentin, PAI-1, MMP-2, calponin) were assessed using Western blotting and qRT-PCR. We assessed the eosinophil, macrophage, and neutrophil profiles in BALs using flow cytometry. Histopathology of lung tissue and collagen deposition were evaluated.

Results: E-cigarette vaping increased p62 accumulation and reduced LC3B-II conversion in lung tissue (p < 0.05 vs. control and PG/VG groups). E-cigarette exposure also significantly increased inflammatory and myogenic profiles. Although the PG/VG group also exhibited elevated inflammation and myogenic responses, they were less dominant than those observed in nicotine vaping groups. Nicotine-exposed lung tissues have increased collagen deposition and inflammatory cell infiltration. Furthermore, the nicotine group showed a significantly higher number of macrophages and eosinophils than the vehicle or PG/VG groups.

Conclusion(s): We found that e-cigarette vaping significantly disrupts lung autophagy in female young adults, indicating impaired autophagic flux. Enhanced inflammation and altered injury repair responses result from this disruption. Furthermore, PG/VG humectants alone increased pulmonary inflammation and fibrotic responses, but to a lesser extent than nicotine-containing vaping. As a result of these findings, we can investigate how e-cigarette exposure during pregnancy impacts lung autophagy, offspring immune development, and pulmonary and inflammatory outcomes.