425 - Impact of Perinatal E-cigarette Exposure on Cardiac Development and Function in Offspring

Publication Number: 425.5545

Virender K. Rehan, Harbor-UCLA Medical Center, Torrance, CA, United States; Sabrina Madrigal, The Lundquist Institute, Monterey Park, CA, United States; Leela Afrose, The Lundquist Institute, Torrance, CA, United States; Ying Wang, The Lundquist Institute, Torrance, CA, United States; Dylan Hatai, UCLA, Los Angeles, CA, United States; Gourav Chandan, Lundquist Institute, Torrance, CA, United States; Noushin Lotfi, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, United States

Background: There is strong evidence indicating an increased risk of cardiovascular disease in offspring with perinatal exposure to cigarette smoke. However, whether perinatal exposure to electronic cigarettes carries similar risks remains uncertain. E-cigarette usage has risen among pregnant women, driven by a misconception of safety. We have previously demonstrated that perinatal nicotine exposure (PNE) leads to increased cardiac extracellular matrix protein deposition, specifically collagen I and III, associated with nicotine's effects on the miR-29 family.

Objective: Here, we utilize a rat model to test the hypothesis that PNE through maternal vaping affects offspring cardiac phenotype by altering MIAT (Myocardial Infarction-Associated Transcript) expression, a long non-coding RNA (lncRNA) known to regulate the miR-29 family.

Design/Methods: Pregnant Sprague-Dawley dams were exposed to filtered air, propylene glycol/vegetable glycol (vehicle) or vehicle+2.4% nicotine via vaping using an established electronic nicotine delivery system. Dams were exposed from embryonic day 6 to postnatal day (PND) 21. Pups were sacrificed at PND21 and PND60, collecting blood and heart at each age. Blood was collected for isolation of lymphocytes and MIAT expression. Histological analysis and molecular studies for lncRNA MIAT, miR29 family, and mesenchymal fibrotic proteins were assessed on heart tissue for each age.

Results: Western blot analysis and qRT-PCR showed expression of ECM related proteins, college III, calponin, fibronectin, increased the perinatal nicotine exposed offspring at both PND21 and PND60, indicating increased fibrosis, i.e., a dysregulated injury repair response. Central Wnt signaling pathway intermediates, β-catenin and Lef1, a key in injury repair, were also increased at PND21 and PND60. Expression of myosin heavy chain 7 (Myh7), although not different at PND21, compared to the control group, was increased at PND 60 in the perinatal nicotine exposed group. Importantly, MIAT expression showed increased trend and miR-29 expression at both PND21 and PND60.

Conclusion(s): These findings show a gradual rise in heart fibrosis marker expression from PND21 to PND60 after PNE via vaping. Increased levels of the lncRNA MIAT, along with decreased expression of the miR-29 family, suggest a possible mechanism for the altered cardiac phenotype linked to PNE. These results further support evidence of compromised cardiac health following PNE, whether through e-cigarette vaping or other sources, and identify potential circulatory biomarkers (MIAT and miR-29) for predicting and monitoring cardiac damage related to PNE.