Abstract 11365: Electronic Cigarette Vaping with or Without Heating Induces Differential Pathological Remodeling in the Lungs and Right Heart

Abstract

Introduction: One of the obstacles in dissecting the specific underlying mechanisms of electronic cigarette (EC) “vaping”-related health effects is the complexity in the chemical composition of EC aerosols. As various chemicals are generated through the heating coil in addition to the intact components presented in the aerosol, we hypothesize that the heating-associated by-products and the intact components would have differential pathological impact to the remodeling of right ventricular (RV) and pulmonary system. Methods: Using a prototype exposure system, C57BL/6 mice were exposed to room air or EC vapor with and without heating the EC liquid (ECL) for 3 hours per day, 5 days per week for 6 months. Echocardiography with color Doppler was used to evaluate cardiac structure and function. To assess inflammatory and fibrotic signaling, Western-blotting was performed. Results: Comparable plasma cotinine levels were found between heating and non-heating exposure, respectively (59.34±8.57ng/mL vs 59.02± 4.83ng/mL; n=5-7). Without heating exposure caused thinning of RV free wall (0.57±0.028 mm control vs 0.43±0.03 mm exposed; p<0.05), whereas with heating, an increase in the RV wall thickness (0.79±0.06 mm exposed, p<0.01) and a reduction in RV chamber size at diastole (1.57±0.04mm control vs 1.34±0.03mm exposed, p<0.01) were observed. While exposure without heating elevates peak pulmonary artery (PA) pressure (2.46±0.31 mmHg control vs 3.34±0.13 mmHg exposed; p<0.05), a lower peak (1.36± 0.12 mmHg exposed; p<0.05) and mean pressure gradient (0.75±0.08 mmHg control vs 0.51± 0.05 mmHg exposed; p<0.05) were recorded with heating exposure. As for pulmonary response, exposure without heating did not affect NF-κB p-p65 level, but reduced p65 expression to 37% of controls (±6%, n=5, p<0.0001) and increased TGF-β1 by 67% (±11%, n=5, p<0.05). In contrast, exposure with heated ECL did not affect p65 and TGF-β1 but increased p-p65/p65 by 39.4% (±5%, n = 5, p < 0.05), indicating activation of NF-κB inflammatory signaling. Conclusions: EC exposure without heating the ECL resulted in fibrotic lung, higher peak PA pressure and RV dystrophy without obvious pulmonary inflammation. Heating the ECL, however, contribute to RV hypertrophy and pulmonary inflammation.