Food and Chemical Toxicology ( IF 4.3 ) Pub Date : 2018-07-17 , DOI: 10.1016/j.fct.2018.07.025 Carine Poussin , Alexandra Laurent , Athanasios Kondylis , Diego Marescotti , Marco van der Toorn , Emmanuel Guedj , Didier Goedertier , Stefano Acali , Claudius Pak , Rémi Dulize , Karine Baumer , Dariusz Peric , Elodie Maluenda , David Bornand , Ignacio Gonzalez Suarez , Walter K. Schlage , Nikolai V. Ivanov , Manuel C. Peitsch , Julia Hoeng
Cigarette smoking causes cardiovascular diseases. Heating tobacco instead of burning it reduces the amount of toxic compounds in the aerosol and may exert a reduced impact on health compared with cigarette smoke. Aqueous extract from the aerosol of a potential modified risk tobacco product, the Carbon Heated Tobacco Product (CHTP) 1.2, was compared in vitro with aqueous extract from the smoke of a 3R4F reference cigarette for its impact on the adhesion of monocytic cells to artery endothelial cells. Human coronary artery endothelial cells (HCAEC) were treated for 4 h with conditioned media from human monocytic Mono Mac 6 (MM6) cells exposed to CHTP1.2 or 3R4F extracts for 2 h or directly with those extracts freshly generated. In vitro monocyte-endothelial cell adhesion was measured concomitantly with inflammatory, oxidative stress, cytotoxicity, and death markers. Furthermore, transcriptomics analyses enabled to quantify the level of perturbation in HCAECs, and provide biological interpretation for the underlying molecular changes following exposure to 3R4F or CHTP1.2 extract. Our systems toxicology study demonstrated that approximately 10–15-fold higher concentrations of the CHTP 1.2 aerosol extract were needed to elicit similar effects as the 3R4F smoke extract on cardiovascular disease-relevant inflammation and cytotoxicity-related mechanisms and markers investigated in vitro.
中文翻译:
基于体外毒理学的潜在改良风险烟草产品CHTP 1.2评估单核细胞粘附于人冠状动脉内皮细胞的血管炎症和细胞毒性相关机制
吸烟会导致心血管疾病。与香烟烟雾相比,加热烟草而不是燃烧烟草可以减少气溶胶中有毒化合物的含量,并且可能对健康产生较小的影响。将来自潜在改良风险烟草产品气雾的水提取物(碳加热烟草产品(CHTP)1.2)与3R4F参比烟的烟雾中的水提取物在体外进行比较,以了解其对单核细胞与动脉内皮细胞粘附的影响细胞。将人冠状动脉内皮细胞(HCAEC)用来自暴露于CHTP1.2或3R4F提取物中的人单核单核Mac 6(MM6)细胞的条件培养基处理2 h,或直接用新鲜产生的提取物处理4 h。体外与炎症,氧化应激,细胞毒性和死亡标志物同时测量单核细胞-内皮细胞粘附。此外,转录组学分析能够量化HCAECs中的扰动水平,并为暴露于3R4F或CHTP1.2提取物后的潜在分子变化提供生物学解释。我们的系统毒理学研究表明,与3R4F烟提取物相比,在体外研究与心血管疾病相关的炎症和与细胞毒性有关的机制和标记物方面,需要大约10-15倍高浓度的CHTP 1.2气溶胶提取物才能引起类似的作用。