E-cigarette exposure with or without heating the e-liquid induces differential remodeling in the lungs and right heart of mice.

Various cardiopulmonary pathologies associated with electronic cigarette (EC) vaping have been reported. This study investigated the differential adverse effects of heating-associated by-products versus the intact components of EC aerosol to the lungs and heart of mice. We further dissected the roles of caspase recruitment domain-containing protein 9 (CARD9)-associated innate immune response and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in EC exposure-induced cardiopulmonary injury. C57BL/6 wild type (WT), CARD9, and NLRP3 mice were exposed to EC aerosol 3 h/day, 5 days/week for 6 month with or without heating the e-liquid with exposure to ambient air as the control. In WT mice, EC exposure with heating (EwH) significantly increased right ventricle (RV) free wall thickness at systole and diastole. However, EC exposure without heating (EwoH) caused a significant decrease in the wall thickness at systole. RV fractional shortening was also markedly reduced following EwH in WT and NLRP3 mice. Further, EwH activated NF-κB and p38 MAPK inflammatory signaling in the lungs, but not in the RV, in a CARD9- and NLRP3-dependent manner. Levels of circulatory inflammatory mediators were also elevated following EwH, indicating systemic inflammation. Moreover, EwoH activated TGF-β1/SMAD2/3/α-SMA fibrosis signaling in the lungs but not the RV of WT mice. In conclusion, EC aerosol exposure following EwH or EwoH induced differential cardiopulmonary remodeling and CARD9 innate immune response and NLRP3 inflammasome contributed to the adverse effects.