Pod-based e-liquids impair human vascular endothelial cell function

Abstract

Pod-based electronic (e-) cigarettes more efficiently deliver nicotine using a protonated formulation. The cardiovascular effects associated with these devices are poorly understood. We evaluated whether pod-based e-liquids and their individual components impair endothelial cell function. We isolated endothelial cells from people who are pod users (n = 10), tobacco never users (n = 7), and combustible cigarette users (n = 6). After a structured use, pod users had lower acetylcholine-mediated endothelial nitric oxide synthase (eNOS) activation compared with never users and was similar to levels from combustible cigarette users (overall P = 0.008, P = 0.01 pod vs never; P = 0.96 pod vs combustible cigarette). The effects of pod-based e-cigarettes and their constituents on vascular cell function were further studied in commercially available human aortic endothelial cells (HAECs) incubated with flavored JUUL e-liquids or propylene glycol (PG):vegetable glycerol (VG) at 30:70 ratio with or without 60 mg/mL nicotine salt for 90 min. A progressive increase in cell death with JUUL e-liquid exposure was observed across 0.0001–1% dilutions; PG:VG vehicle with and without nicotine salt induced cell death. A23187-stimulated nitric oxide production was decreased with all JUUL e-liquid flavors, PG:VG and nicotine salt exposures. Aerosols generated by JUUL e-liquid heating similarly decreased stimulated nitric oxide production. Only mint flavored e-liquids increased inflammation and menthol flavored e-liquids enhanced oxidative stress in HAECs. In conclusion, pod e-liquids and their individual components appear to impair endothelial cell function. These findings indicate the potential harm of pod-based devices on endothelial cell function and thus may be relevant to cardiovascular injury in pod type e-cigarette users.

Vanadium Carbide MXenzyme Harnessing Photothermal Effects for Targeted Lung Tumor Suppression and Inflammation Eradication

“…POD is an antioxidant enzyme that catalyzes the breakdown of H 2 O 2 into H 2 O and O 2 . [ 29 ] The POD‐like activity of V 2 C MXenzyme was assessed using 3,3′,5,5′‐tetramethylbenzidine (TMB) as the chromogenic substrate. In the presence of TMB, V 2 C MXenzyme catalyzed the conversion of H 2 O 2 to H 2 O, with a time‐dependent increase in absorption at 652 nm (Figure 4I).…”

Chronic Pod-Mod E-Cigarette Aerosol Exposure Induces Aortic Dysfunction in Hypercholesterolemic Mice: Role of Oxidative Stress and Inflammation

“…21 Complementary to this evidence, endothelial nitric oxide synthase (eNOS) phosporylation 22 and nitric oxide (NO) production 20 are blunted in venous endothelial cells from e-cigarette users. Human umbilical vein endothelial cells (HUVECs) cultured with serum from e-cigarette users 21 and human aortic endothelial cells (HAECs) incubated with e-liquids 22 likewise secrete less NO. Exposure to e-cigarette aerosol extract 23 and e-cigarette user serum 21 further induces production of reactive oxygen species (ROS) in cultured HUVECs.…”

“…17, 18 Habitual e-cigarette users experience systemic oxidative stress, 19 radial artery stiffening, 20 and reduced brachial artery flow-mediated dilatation. 21 Complementary to this evidence, endothelial nitric oxide synthase (eNOS) phosporylation 22 and nitric oxide (NO) production 20 are blunted in venous endothelial cells from e-cigarette users. Human umbilical vein endothelial cells (HUVECs) cultured with serum from e-cigarette users 21 and human aortic endothelial cells (HAECs) incubated with e-liquids 22 likewise secrete less NO.…”

“…Complementary to our findings, Majid et al recently reported that venous endothelial cells isolated from pod-mod e-cigarette users exhibit decreased eNOS phosphorylation in response to acetylcholine compared to never users, and that human aortic endothelial cells exposed to pod-mod e-liquids produce less NO following calcium ionophore stimulation, further im-plicating limited eNOS activation as a source of vaping-induced NO deficiency. 22 Alongside reduced eNOS expression and/or activation, excess superoxide anion within the aortic wall may lower NO levels by reacting with the compound to form peroxynitrite. Paralleling observations in prior generation e-cigarette users 19 as well as exposed mice, 28,27 repeated inhalation of pod-mod e-cigarette aerosol increases the oxidative burden both systemically (Figure 3G) and within aortic tissues (Figure 3A-B,F).…”

“…Complementary to our findings, Majid et al recently reported that venous endothelial cells isolated from pod-mod e-cigarette users exhibit decreased eNOS phosphorylation in response to acetylcholine compared to never users, and that human aortic endothelial cells exposed to pod-mod e-liquids produce less NO following calcium ionophore stimulation, further implicating limited eNOS activation as a source of vaping-induced NO deficiency. 22…”