Cirillo Plinio, Morello Mariarosaria, Titolo Gisella, Marra Laura, Morello Andrea, De Rosa Gennaro, Cozzolino Domenico, Sugraliyev Akhmetzhan, Cimmino Giovanni
Department of Advanced Biomedical Sciences, Division of Cardiology, University of Naples "Federico II", Via Pansini, 5, Naples, 80131, Italy.
Department of Translational Medical Sciences, Section of Cardiology, University of Campania "Luigi Vanvitelli", Naples, Italy.
J Thromb Thrombolysis. 2025 Jan;58(1):62-70. doi: 10.1007/s11239-024-03018-6. Epub 2024 Aug 29.
E-cigarettes (ECIG) are proposed as an alternative for regular tobacco users with less dangerous effects for health. Several studies demonstrated that ECIG exert deleterious cardiovascular effects and promote platelet dependent thrombosis. However, ECIG role on Tissue Factor-dependent thrombosis is still unknown. Dysfunctional endothelial cells (ECs) are known to express Tissue Factor (TF) on their surface. Aim of the present study was to investigate whether ECIG might promote TF expression in ECs, shifting them to a pro thrombotic phenotype.
Human Umbilical Vein Endothelial Cells (HUVEC) were incubated with increasing doses of ECIG (commercially available and mix of propylene glycol/vegetable glycerine/nicotine 18 mg/mL) up to 1.8 mg/mL. TF gene expression and protein levels were assessed at different time points by Real Time PCR and Western Blot, respectively. TF surface expression and activity were also measured by FACS analysis and coagulation assay. Finally, NF-kB translocation was investigated as possible mechanism of action. Potential protective effects by Rosuvastatin were also investigated.
ECIG significantly increased TF expression at both gene and protein levels in a time and dose dependent manner. Surface expression and procoagulant activity were increased as well. These phenomena appeared modulated by the NF-κB pathway. Rosuvastatin reduced ECIG effects on TF-mRNA.
Although in vitro, we indicate that ECIG promote a pro thrombotic phenotype in ECs via expression of functional TF. Data of the present study permit to shed a brighter light on the still partially unresolved issue about the role of ECIG in development of cardiovascular diseases suggesting that they might represent a potential risk factor for thrombotic cardiovascular events.
电子烟被提议作为普通烟草使用者的替代品，对健康危害较小。多项研究表明，电子烟会产生有害的心血管影响并促进血小板依赖性血栓形成。然而，电子烟对组织因子依赖性血栓形成的作用仍不清楚。已知功能失调的内皮细胞（ECs）在其表面表达组织因子（TF）。本研究的目的是调查电子烟是否可能促进内皮细胞中TF的表达，使其转变为促血栓形成表型。
将人脐静脉内皮细胞（HUVEC）与剂量不断增加的电子烟（市售，丙二醇/蔬菜甘油/尼古丁混合物，18毫克/毫升）孵育，最高浓度达1.8毫克/毫升。分别通过实时聚合酶链反应和蛋白质印迹法在不同时间点评估TF基因表达和蛋白质水平。还通过荧光激活细胞分选分析和凝血试验测量TF表面表达和活性。最后，研究核因子-κB（NF-κB）易位作为可能的作用机制。还研究了瑞舒伐他汀的潜在保护作用。
电子烟以时间和剂量依赖性方式显著增加TF在基因和蛋白质水平的表达。表面表达和促凝血活性也增加。这些现象似乎受NF-κB途径调节。瑞舒伐他汀降低了电子烟对TF-mRNA的影响。
尽管是在体外研究，但我们表明电子烟通过功能性TF的表达促进内皮细胞形成促血栓形成表型。本研究数据有助于更清楚地了解电子烟在心血管疾病发展中作用这一仍未完全解决的问题，表明它们可能是血栓性心血管事件的潜在危险因素。
