利用人诱导多能干细胞衍生的内皮细胞建立电子烟心血管风险模型。
Modeling Cardiovascular Risks of E-Cigarettes With Human-Induced Pluripotent Stem Cell-Derived Endothelial Cells.
机构信息
Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California; Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, Arizona.
Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California; Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois; Division of Cardiology, Department of Medicine, University of Illinois College of Medicine, Chicago, Illinois.
出版信息
J Am Coll Cardiol. 2019 Jun 4;73(21):2722-2737. doi: 10.1016/j.jacc.2019.03.476.
BACKGROUND
Electronic cigarettes (e-cigarettes) have experienced a tremendous increase in use. Unlike cigarette smoking, the effects of e-cigarettes and their constituents on mediating vascular health remain understudied. However, given their increasing popularity, it is imperative to evaluate the health risks of e-cigarettes, including the effects of their ingredients, especially nicotine and flavorings.
OBJECTIVES
The purpose of this study was to investigate the effects of flavored e-cigarette liquids (e-liquids) and serum isolated from e-cigarette users on endothelial health and endothelial cell-dependent macrophage activation.
METHODS
Human-induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) and a high-throughput screening approach were used to assess endothelial integrity following exposure to 6 different e-liquids with varying nicotine concentrations and to serum from e-cigarette users.
RESULTS
The cytotoxicity of the e-liquids varied considerably, with the cinnamon-flavored product being most potent and leading to significantly decreased cell viability, increased reactive oxygen species (ROS) levels, caspase 3/7 activity, and low-density lipoprotein uptake, activation of oxidative stress-related pathway, and impaired tube formation and migration, confirming endothelial dysfunction. Upon exposure of ECs to e-liquid, conditioned media induced macrophage polarization into a pro-inflammatory state, eliciting the production of interleukin-1β and -6, leading to increased ROS. After exposure of human iPSC-ECs to serum of e-cigarette users, increased ROS linked to endothelial dysfunction was observed, as indicated by impaired pro-angiogenic properties. There was also an observed increase in inflammatory cytokine expression in the serum of e-cigarette users.
CONCLUSIONS
Acute exposure to flavored e-liquids or e-cigarette use exacerbates endothelial dysfunction, which often precedes cardiovascular diseases.
背景
电子烟的使用量大幅增加。与吸烟不同，电子烟及其成分对血管健康的影响仍在研究之中。然而，鉴于电子烟越来越受欢迎，评估电子烟的健康风险至关重要，包括其成分（尤其是尼古丁和调味剂）的影响。
目的
本研究旨在研究调味电子烟液（e-liquid）和电子烟使用者血清对内皮健康和内皮细胞依赖性巨噬细胞激活的影响。
方法
使用人诱导多能干细胞衍生的内皮细胞（iPSC-ECs）和高通量筛选方法，评估 6 种不同尼古丁浓度电子烟液和电子烟使用者血清暴露后内皮完整性的变化。
结果
电子烟液的细胞毒性差异很大，肉桂味产品的毒性最强，导致细胞活力显著下降、活性氧（ROS）水平升高、半胱天冬酶 3/7 活性增加、低密度脂蛋白摄取增加、氧化应激相关途径激活以及管形成和迁移受损，证实了内皮功能障碍。ECs 暴露于电子烟液后，条件培养基诱导巨噬细胞向促炎状态极化，引起白细胞介素-1β和白细胞介素-6 的产生，导致 ROS 增加。在将人 iPSC-ECs 暴露于电子烟使用者的血清后，观察到与内皮功能障碍相关的 ROS 增加，表现为促血管生成特性受损。电子烟使用者血清中也观察到炎症细胞因子表达增加。
结论
急性暴露于调味电子烟液或电子烟使用会加剧内皮功能障碍，而内皮功能障碍常常是心血管疾病的前兆。
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