Division of Cardiology (L.M., D.D.H., R.D., P.R., P.G., M.L.S.), University of California, San Francisco.
Now with School of Medicine and Dentistry, University of Rochester, NY (D.D.H.).
Arterioscler Thromb Vasc Biol. 2022 Nov;42(11):1333-1350. doi: 10.1161/ATVBAHA.121.317749. Epub 2022 Oct 26.
The harmful vascular effects of smoking are well established, but the effects of chronic use of electronic cigarettes (e-cigarettes) on endothelial function are less understood. We hypothesized that e-cigarette use causes changes in blood milieu that impair endothelial function.
Endothelial function was measured in chronic e-cigarette users, chronic cigarette smokers, and nonusers. We measured effects of participants' sera, or e-cigarette aerosol condensate, on NO and HO release and cell permeability in cultured endothelial cells (ECs).
E-cigarette users and smokers had lower flow-mediated dilation (FMD) than nonusers. Sera from e-cigarette users and smokers reduced VEGF (vascular endothelial growth factor)-induced NO secretion by ECs relative to nonuser sera, without significant reduction in endothelial NO synthase mRNA or protein levels. E-cigarette user sera caused increased endothelial release of HO, and more permeability than nonuser sera. E-cigarette users and smokers exhibited changes in circulating biomarkers of inflammation, thrombosis, and cell adhesion relative to nonusers, but with distinct profiles. E-cigarette user sera had higher concentrations of the receptor for advanced glycation end products (RAGE) ligands S100A8 and HMGB1 (high mobility group box 1) than smoker and nonuser sera, and receptor for advanced glycation end product inhibition reduced permeability induced by e-cigarette user sera but did not affect NO production.
Chronic vaping and smoking both impair FMD and cause changes in the blood that inhibit endothelial NO release. Vaping, but not smoking, causes changes in the blood that increase microvascular endothelial permeability and may have a vaping-specific effect on intracellular oxidative state. Our results suggest a role for RAGE in e-cigarette-induced changes in endothelial function.
吸烟对血管的有害影响已得到充分证实，但慢性使用电子烟（电子烟）对内皮功能的影响则知之甚少。我们假设电子烟的使用会改变血液环境，从而损害内皮功能。
我们测量了慢性电子烟使用者、慢性吸烟者和非使用者的内皮功能。我们测量了参与者的血清或电子烟气溶胶冷凝物对培养的内皮细胞（ECs）中 NO 和 HO 释放和细胞通透性的影响。
电子烟使用者和吸烟者的血流介导的扩张（FMD）低于非使用者。与非使用者的血清相比，电子烟使用者和吸烟者的血清降低了血管内皮生长因子（VEGF）诱导的 ECs 中 NO 的分泌，而内皮型一氧化氮合酶 mRNA 或蛋白水平没有明显降低。电子烟使用者的血清引起内皮 HO 的释放增加和通透性增加，超过非使用者的血清。与非使用者相比，电子烟使用者和吸烟者表现出循环炎症、血栓形成和细胞黏附生物标志物的变化，但具有不同的特征。与吸烟者和非使用者的血清相比，电子烟使用者的血清中晚期糖基化终产物（RAGE）配体 S100A8 和 HMGB1（高迁移率族蛋白 B1）的受体浓度更高，而 RAGE 受体抑制可减少电子烟使用者的血清引起的通透性，但不影响 NO 的产生。
慢性吸电子烟和吸烟都会损害 FMD，并导致血液发生变化，从而抑制内皮细胞 NO 的释放。吸电子烟会引起血液变化，增加微血管内皮通透性，并且可能对细胞内氧化状态产生电子烟特有的影响。我们的结果表明 RAGE 在电子烟引起的内皮功能变化中起作用。
