PDF(Pubmed)
Abstract：
The purpose of this study was to determine the effect of circulating microvesicles isolated from chronic electronic (e-)cigarette users on cultured human umbilical vein endothelial cell (HUVEC) expression of nuclear factor-κB (NF-κB), cellular cytokine release, phosphorylation of endothelial nitric oxide synthase (eNOS) and NO production. The HUVECs were treated with microvesicles isolated via flow cytometry from nine non-tobacco users (five male and four female; 22 ± 2 years of age) and 10 e-cigarette users (six male and four female; 22 ± 2 years of age). Microvesicles from e-cigarette users induced significantly greater release of interleukin-6 (183.4 ± 23.6 vs. 150.6 ± 15.4 pg/mL; P = 0.002) and interleukin-8 (160.0 ± 31.6 vs. 129.4 ± 11.2 pg/mL; P = 0.01), in addition to expression of p-NF-κB p65 (Ser536) (18.8 ± 3.4 vs. 15.6 ± 1.5 a.u.; P = 0.02) from HUVECs compared with microvesicles from non-tobacco users. Nuclear factor-κB p65 was not significantly different between microvesicles from the non-tobacco users and from the e-cigarette users (87.6 ± 8.7 vs. 90.4 ± 24.6 a.u.; P = 0.701). Neither total eNOS (71.4 ± 21.8 vs. 80.4 ± 24.5 a.u.; P = 0.413) nor p-eNOS (Thr495) (229.2 ± 26.5 vs. 222.1 ± 22.7 a.u.; P = 0.542) was significantly different between microvesicle-treated HUVECs from non-tobacco users and e-cigarette users. However, p-eNOS (Ser1177) (28.9 ± 6.2 vs. 45.8 ± 9.0 a.u.; P < 0.001) expression was significantly lower from e-cigarette users compared with non-tobacco users. Nitric oxide production was significantly lower (8.2 ± 0.6 vs. 9.7 ± 0.9 μmol/L; P = 0.001) in HUVECs treated with microvesicles from e-cigarette users compared with microvesicles from non-tobacco users. This study demonstrated increased NF-κB activation and inflammatory cytokine production, in addition to diminished eNOS activity and NO production resulting from e-cigarette use. HIGHLIGHTS: What is the central question of this study? Circulating microvesicles contribute to cardiovascular health and disease via their effects on the vascular endothelium. The impact of electronic (e-)cigarette use on circulating microvesicle phenotype is not well understood. What is the main finding and its importance? Circulating microvesicles from e-cigarette users increase endothelial cell inflammation and impair endothelial nitric oxide production. Endothelial inflammation and diminished nitric oxide bioavailability are central factors underlying endothelial dysfunction and, in turn, cardiovascular disease risk. Deleterious changes in the functional phenotype of circulating microvesicles might contribute to the reported adverse effects of e-cigarette use on cardiovascular health.
摘要：
这项研究的目的是确定从慢性电子（e）香烟使用者中分离的循环微泡对培养的人脐静脉内皮细胞（HUVEC）表达核因子-κB（NF-κB）的影响，细胞细胞因子释放，内皮型一氧化氮合酶（eNOS）的磷酸化和NO的产生。用流式细胞术从9名非烟草使用者(5名男性和4名女性;22±2岁)和10名电子烟使用者(6名男性和4名女性;22±2岁)分离的微泡处理HUVEC。电子烟使用者的微泡诱导白细胞介素6的释放显着增加（183.4±23.6与150.6±15.4pg/mL；P=0.002）和白细胞介素8（160.0±31.6vs.129.4±11.2pg/mL；P=0.01），除p-NF-κBp65（Ser536）的表达外（18.8±3.4vs.15.6±1.5a.u.；P=0.02）来自HUVEC，与非烟草使用者的微泡相比。非烟草使用者和电子烟使用者的微泡之间的核因子-κBp65没有显着差异（87.6±8.7vs.90.4±24.6a.u.；P=0.701）。总eNOS(71.4±21.8与80.4±24.5a.u.；P=0.413）或p-eNOS（Thr495）（229.2±26.5vs.222.1±22.7a.u.;P=0.542）在非烟草使用者和电子烟使用者的微泡处理的HUVEC之间存在显着差异。然而,p-eNOS(Ser1177)(28.9±6.2vs.45.8±9.0a.u.;P<0.001）与非烟草使用者相比，电子烟使用者的表达显着降低。一氧化氮的产量显着降低（8.2±0.6vs.9.7±0.9μmol/L；P=0.001）在用电子烟使用者的微泡处理的HUVEC中，与非烟草使用者的微泡相比。这项研究表明NF-κB活化和炎性细胞因子产生增加，除了减少的eNOS活性和NO产生导致电子烟的使用。摘要：这项研究的中心问题是什么？循环微泡通过对血管内皮的影响而促进心血管健康和疾病。电子(e-)香烟使用对循环微泡表型的影响还没有很好地理解。主要发现及其重要性是什么？电子烟使用者的循环微泡会增加内皮细胞炎症并损害内皮一氧化氮的产生。内皮炎症和一氧化氮生物利用度降低是内皮功能障碍的主要因素，反过来,心血管疾病的风险。循环微泡功能表型的有害变化可能有助于报告的电子烟使用对心血管健康的不利影响。
