Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures

Abstract

The increased use of inhaled nicotine via e-cigarettes has unknown risks to lung health. Having previously shown that cigarette smoke (CS) extract disrupts the lung microvasculature barrier function by endothelial cell activation and cytoskeletal rearrangement, we investigated the contribution of nicotine in CS or e-cigarettes (e-Cig) to lung endothelial injury. Primary lung microvascular endothelial cells were exposed to nicotine, e-Cig solution, or condensed e-Cig vapor (1-20 mM nicotine) or to nicotine-free CS extract or e-Cig solutions. Compared with nicotine-containing extract, nicotine free-CS extract (10-20%) caused significantly less endothelial permeability as measured with electric cell-substrate impedance sensing. Nicotine exposures triggered dose-dependent loss of endothelial barrier in cultured cell monolayers and rapidly increased lung inflammation and oxidative stress in mice. The endothelial barrier disruptive effects were associated with increased intracellular ceramides, p38 MAPK activation, and myosin light chain (MLC) phosphorylation, and was critically mediated by Rho-activated kinase via inhibition of MLC-phosphatase unit MYPT1. Although nicotine at sufficient concentrations to cause endothelial barrier loss did not trigger cell necrosis, it markedly inhibited cell proliferation. Augmentation of sphingosine-1-phosphate (S1P) signaling via S1P1 improved both endothelial cell proliferation and barrier function during nicotine exposures. Nicotine-independent effects of e-Cig solutions were noted, which may be attributable to acrolein, detected along with propylene glycol, glycerol, and nicotine by NMR, mass spectrometry, and gas chromatography, in both e-Cig solutions and vapor. These results suggest that soluble components of e-Cig, including nicotine, cause dose-dependent loss of lung endothelial barrier function, which is associated with oxidative stress and brisk inflammation.

Will chronic e-cigarette use cause lung disease?

“…Cytotoxicity [31] , Cell viability [31] , Inflammation [94,159] , Infection [159] Cytotoxicity [10,94] , Cell viability [10,94] , Altered morphology [94] Cell viability [133] , Electrical resistance [133] Macrophages [142] , Cytokine secretion [31] , Infection [159] SCC Epithelia Current knowledge of the effects of E-cigarette (E-Cig) and e-liquid exposures on pulmonary cell types. Included in the table is a short list of the current in vitro and in vivo study outcomes for lung-related cell types that are depicted in the cartoon and labeled appropriately.…”

Short‐Term E‐Cigarette Exposure Increases the Risk of Thrombogenesis and Enhances Platelet Function in Mice

“…Furthermore, some of these studies were contradictory, with some reporting no cardiovascular harm,11, 12 whereas others found e‐cigarettes to be harmful 13, 14. In support of the latter notion, several studies have shown that e‐cigarettes are associated with an increase in blood pressure, aortic stiffness, endothelial dysfunction, and oxidative stress 6, 13, 14, 15. Interestingly, a recent study reported that e‐cigarette–induced impairment of cardiovascular function in mice was similar to that triggered by conventional smoking, in which a comparable increase in aortic stiffness was observed 14…”

Acute effects of short term use of e-cigarettes on airways physiology and respiratory symptoms in smokers with and without airways obstructive diseases and in healthy non smokers

“…It is also cytotoxic, induces apoptosis in fibroblats 8 , initiate inflammation at Kupffer 9 and enthothelial 10 cells, and alters vascular smooth muscle cells 11 . There is also an increasing number of studies in animal models implicating possible health effects.…”