Abstract Body: Introduction/Background
Electronic cigarette (e-cig) use is increasing among adolescents as an introduction to nicotine rather than a smoking cessation tool. As individuals who vape reach reproductive age, continued use during pregnancy is a growing concern. While prenatal tobacco exposure is associated with adverse cardiac outcomes, the effects of inhaled e-cig aerosols containing nicotine remain poorly defined. In addition, e-cig devices delivering tetrahydrocannabinol (THC) are growing in popularity, yet the developmental risks of prenatal THC exposure are not well understood.
Hypothesis
We assessed the hypothesis that prenatal e-cig exposure induces early cardiac remodeling in offspring, characterized by increased collagen deposition and fibroblast activation.
Methods
Female C57BL/6 mice were exposed to aerosolized e-cig vapor containing 5 mg/mL nicotine or vehicle control for 4 weeks prior to breeding and continued throughout gestation. Exposure was terminated at birth, and offspring hearts were collected at postnatal day (PD) 21. Cardiac collagen deposition was assessed by histology. Timed-pregnant Sprague-Dawley rats were exposed to aerosolized nicotine (36 mg/mL), THC (100 mg/mL), nicotine plus THC, or vehicle control from gestational days 5-20. Offspring hearts were collected at PD31 and assessed for collagen deposition by histology and fibroblast-specific protein 1 (FSP1) expression by immunostaining. Group comparisons were performed using one-way ANOVA with Tukey’s multiple comparisons test.
Results
In mice, prenatal nicotine exposure increased collagen deposition at PD21 by ~1.5-fold (n=3 control, n=7 nicotine; p<0.05). In rats, prenatal nicotine exposure increased cardiac collagen deposition at PD31 by ~2-fold vs control (n=6 control, n=7 nicotine; p<0.01), with similar increases in the nicotine plus THC group (n=8; p<0.001), whereas THC alone did not differ from control (n=13). Nicotine-exposed PD31 rat hearts also exhibited increased FSP1 expression (p<0.05), consistent with fibroblast activation.
Conclusions
Prenatal exposure to e-cig aerosols containing nicotine induces early cardiac remodeling characterized by collagen accumulation and fibroblast activation, consistent with a nicotine-mediated effect that is not observed with THC alone. These findings identify potential cardiovascular risks of e-cig use during pregnancy and support further mechanistic investigation.