Aerosolized nicotine-free e-liquid base constituents exacerbates mitochondrial dysfunction and endothelial glycocalyx shedding via the AKT/GSK3β-mPTP pathway in lung injury models

作者：Ziyu Dai, Bin Xie, Jiang Chen, Yun Peng, Jianing Lin, Qiong Chen, Jingyi Sun · 发表于：Respiratory Research · 年份：2025 · DOI：10.1186/s12931-025-03155-3 · 被引用次数：10 · 研究领域：Trauma, Hemostasis, Coagulopathy, Resuscitation、Cardiac Arrest and Resuscitation、Traumatic Brain Injury and Neurovascular Disturbances

Smoking has been recognized as a risk factor of cancer, heart disease, stroke, diabetes, and lung diseases such as chronic obstructive pulmonary disease, and nicotine appears to be the responsible component of tobacco smoke that affects lung development. While nicotine-free electronic cigarettes (e-cigarettes) are often promoted as a safer alternative to traditional smoking, recent evidence suggests that they might pose significant health risks. This study investigates the effects of nicotine-free e-cigarette vapor (ECV) on lung tissue and endothelial function. A mouse model of ECV-induced lung injury and human pulmonary microvascular endothelial cells (HPMVECs) were utilized to evaluate the impact of ECV exposure on mitochondrial function, endothelial cell viability, and glycocalyx shedding. ECV exposure significantly damages lung tissue, characterized by alveolar enlargement, inflammation, and vascular remodeling, indicative of emphysematous changes. In vitro, HPMVECs exposed to nicotine-free e-cigarette extract (ECE) demonstrated dose-dependent increases in mitochondrial reactive oxygen species (ROS), mitochondrial membrane depolarization, mPTP opening, and reduced ATP production, leading to enhanced endothelial permeability and glycocalyx degradation. The inhibition of mPTP opening with Cyclosporin A (CsA) was found to mitigate the mitochondrial dysfunction and glycocalyx damage induced by ECE, indicating a protective role of mPTP inhibition in preserving endothelial inte...