Maternal third hand exposure to e-cigarette vapor alters lung and bone marrow immune cell responses in offspring in the absence or presence of flu infection.

There is increasing evidence that third hand exposure to e-cigarette vapor (e-vapor) can have detrimental effects on the lungs. However, whether maternal exposure during pregnancy results in harmful changes to the offspring is unknown. Using two different e-cigarette settings (low versus high power), BALB/c mice were subjected to third hand e-vapor (e-vapor deposited onto towels, towels changed daily) in the absence or presence of nicotine, before, during, and after pregnancy. Male adult offspring were then infected with mouse-adapted influenza A virus (A/PR/8/34 H1N1) and lung and bone marrow immune cell responses assessed 7 days post infection. Maternal third hand exposure to low power (MLP) or high power (MHP) e-vapor with nicotine (MLP+NIC and MHP+NIC, respectively) increased the percentage of lung immune cells and neutrophils in the bone marrow. Interestingly, Flu-infected offspring from MLP+NIC and MHP+NIC groups had lower percentages of lung alveolar macrophages, and more pronounced increases in neutrophils in the bone marrow, when compared to offspring from MSham Flu controls. Flu infection also decreased the percentage of lung CD4+ T cells and increased the percentage of lung CD8+ T cells, irrespective of maternal exposure (MLP-/+NIC and MHP-/+NIC). Significantly, both MLP+NIC and MHP+NIC resulted in blunted activation of lung CD4+ T cells, but only MLP+NIC caused blunted activation of lung CD8+ T cells. Together, we show for the first time that maternal third hand exposure to e-vapor results in significant, long-lived effects on lung and bone marrow immune cell responses in offspring at baseline and in response to Flu infection.

The impact of airborne particulate matter-based pollution on the cellular and molecular mechanisms in chronic obstructive pulmonary disease (COPD).

Inhalation of particulate matter (PM), one of the many components of air pollution, is associated with the development and exacerbation of chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD). COPD is one of the leading causes of global mortality and morbidity, with a paucity of therapeutic options and a significant contributor to global health expenditure. This review aims to provide a mechanistic understanding of the cellular and molecular pathways that lead to the development of COPD following chronic PM exposure. Our review describes how the inhalation of PM can lead to lung parenchymal destruction and cellular senescence due to chronic pulmonary inflammation and oxidative stress. Following inhalation of PM, significant increases in a range of pro-inflammatory cytokines, mediated by the nuclear factor kappa B pathway are reported. This review also highlights how the inhalation of PM can lead to deleterious chronic oxidative stress persisting in the lung post-exposure. Furthermore, our work summarises how PM inhalation can lead to airway remodelling, with increases in pro-fibrotic cytokines and collagen deposition, typical of COPD. This paper also accentuates the interconnection and possible synergism between the pathophysiological mechanisms leading to COPD. Our work emphasises the serious health consequences of PM exposure on respiratory health. Elucidation of the cellular and molecular mechanisms can provide insight into possible therapeutic options. Finally, this review should serve as a stark reminder of the need for genuine action on air pollution to decrease the associated health burden on our growing global population.

Chronic maternal exposure to low-dose PM2.5 impacts cognitive outcomes in a sex-dependent manner.

There is no safe level of air pollution for human health. Traffic-related particulate matter (PM2.5) is a major in-utero toxin, mechanisms of action of which are not fully understood. BALB/c dams were exposed to an Australian level of traffic PM2.5 (5 µg/mouse/day, intranasal, 6 weeks before mating, during gestation and lactation). Male offspring had reduced memory in adulthood, whereas memory was normal in female littermates, similar to human responses. Maternal PM2.5 exposure resulted in oxidative stress and abnormal mitochondria in male, but not female, brains. RNA-sequencing analysis showed unique sex-related changes in newborn brains. Two X-chromosome-linked histone lysine demethylases, Kdm6a and Kdm5c, demonstrated higher expression in female compared to male littermates, in addition to upregulated genes with known functions to support mitochondrial function, synapse growth and maturation, cognitive function, and neuroprotection. No significant changes in Kdm6a and Kdm5c were found in male littermates, nor other genes, albeit significantly impaired memory function after birth. In primary foetal cortical neurons, PM2.5 exposure suppressed neuron and synaptic numbers and induced oxidative stress, which was prevented by upregulation of Kdm6a or Kdm5c. Therefore, timely epigenetic adaptation by histone demethylation to open DNA for translation before birth may be the key to protecting females against prenatal PM2.5 exposure-induced neurological disorders, which fail to occur in males associated with their poor cognitive outcomes.

To burn or not to burn: similar effects of different types of prenatal tobacco exposure on infant lung function.

The first study to describe the harmful effects of snus on the unborn infant provides evidence to help clinicians and mothers collectively to make an informed choice about quitting the use of snus before planning pregnancies https://bit.ly/3vJnBxW.

The Lungs in Space: A Review of Current Knowledge and Methodologies.

Space travel presents multiple risks to astronauts such as launch, radiation, spacewalks or extravehicular activities, and microgravity. The lungs are composed of a combination of air, blood, and tissue, making it a complex organ system with interactions between the external and internal environment. Gravity strongly influences the structure of the lung which results in heterogeneity of ventilation and perfusion that becomes uniform in microgravity as shown during parabolic flights, Spacelab, and Skylab experiments. While changes in lung volumes occur in microgravity, efficient gas exchange remains and the lungs perform as they would on Earth; however, little is known about the cellular response to microgravity. In addition to spaceflight and real microgravity, devices, such as clinostats and random positioning machines, are used to simulate microgravity to study cellular responses on the ground. Differential expression of cell adhesion and extracellular matrix molecules has been found in real and simulated microgravity. Immune dysregulation is a known consequence of space travel that includes changes in immune cell morphology, function, and number, which increases susceptibility to infections. However, the majority of in vitro studies do not have a specific respiratory focus. These studies are needed to fully understand the impact of microgravity on the function of the respiratory system in different conditions.

Homeostatic Measure of Insulin Resistance Is Associated With Future Asthma Exacerbations: A 1-Year Prospective Cohort Study.

BACKGROUND: Recent evidence suggests that insulin resistance affects asthma outcomes. However, the effect of the homeostatic measure of insulin resistance (HOMA-IR) on airway inflammation and asthma exacerbations (AEs) is poorly understood. OBJECTIVE: To analyze the relationship between HOMA-IR and clinical and inflammatory characteristics in patients with asthma, and the association between HOMA-IR and AEs in the following year. METHODS: A prospective cohort study recruited participants with asthma, who were classified into the HOMA-IRhigh group and HOMA-IRlow group based on the cutoff value of 3.80 for HOMA-IR and were observed within 12 months. We evaluated the clinical and inflammatory features and conducted a 1-year follow-up to study the exacerbations. We used negative binomial regression models to analyze the association between HOMA-IR and AEs. RESULTS: Compared with patients in the HOMA-IRlow group (n = 564), those in the HOMA-IRhigh group (n = 61) had higher levels of body mass index, a higher waist circumference and waist-hip ratio, higher triglycerides, lower cholesterol high-density lipoproteins, more neutrophils in the peripheral blood, and elevated IL-5 levels in the induced sputum. Furthermore, patients in the HOMA-IRhigh group had a significantly increased risk for moderate to severe AEs (adjusted incidence rate ratio [aIRR] = 2.26; 95% CI, 1.38-3.70), severe AEs (aIRR = 2.42; 95% CI, 1.26-4.67), hospitalization (aIRR = 2.54; 95% CI, 1.20-5.38), and emergency visits (aIRR = 3.04; 95% CI, 1.80-8.53). CONCLUSIONS: The homeostatic measure of insulin resistance was associated with asthma-related clinical features and airway inflammation, and was an independent risk factor for future AEs. Therefore, insulin resistance may have important implications for managing asthma as a potential treatable trait.

Computational and biological approaches in repurposing ribavirin for lung cancer treatment: Unveiling antitumorigenic strategies.

Lung cancer is among leading causes of death worldwide. The five-year survival rate of this disease is extremely low (17.8 %), mainly due to difficult early diagnosis and to the limited efficacy of currently available chemotherapeutics. This underlines the necessity to develop innovative therapies for lung cancer. In this context, drug repurposing represents a viable approach, as it reduces the turnaround time of drug development removing costs associated to safety testing of new molecular entities. Ribavirin, an antiviral molecule used to treat hepatitis C virus infections, is particularly promising as repurposed drug for cancer treatment, having shown therapeutic activity against glioblastoma, acute myeloid leukemia, and nasopharyngeal carcinoma. In the present study, we thoroughly investigated the in vitro anticancer activity of ribavirin against A549 human lung adenocarcinoma cells. From a functional standpoint, ribavirin significantly inhibits cancer hallmarks such as cell proliferation, migration, and colony formation. Mechanistically, ribavirin downregulates the expression of numerous proteins and genes regulating cell migration, proliferation, apoptosis, and cancer angiogenesis. The anticancer potential of ribavirin was further investigated in silico through gene ontology pathway enrichment and protein-protein interaction networks, identifying five putative molecular interactors of ribavirin (Erb-B2 Receptor Tyrosine Kinase 4 (Erb-B4); KRAS; Intercellular Adhesion Molecule 1 (ICAM-1); amphiregulin (AREG); and neuregulin-1 (NRG1)). These interactions were characterized via molecular docking and molecular dynamic simulations. The results of this study highlight the potential of ribavirin as a repurposed chemotherapy against lung cancer, warranting further studies to ascertain the in vivo anticancer activity of this molecule.

Activated non-neuronal cholinergic system correlates with non-type 2 inflammation and exacerbations in severe asthma.

BACKGROUND: Non-neuronal cholinergic system (NNCS) contributes to various inflammatory airway diseases. However, the role of NNCS in severe asthma (SA) remains largely unexplored. OBJECTIVE: To explore airway NNCS in SA. METHODS: In this prospective cohort study based on the Australasian Severe Asthma Network in a real-world setting, patients with SA (n = 52) and non-SA (n = 104) underwent clinical assessment and sputum induction. The messenger RNA (mRNA) levels of NNCS components and proinflammatory cytokines in the sputum were detected using real-time quantitative polymerase chain reaction, and the concentrations of acetylcholine (Ach)-related metabolites were evaluated using liquid chromatography coupled with tandem mass spectrometry. Asthma exacerbations were prospectively investigated during the next 12 months. The association between NNCS and future asthma exacerbations was also analyzed. RESULTS: Patients with SA were less controlled and had worse airway obstruction, a lower bronchodilator response, higher doses of inhaled corticosteroids, and more add-on treatments. The sputum mRNA levels of NNCS components, such as muscarinic receptors M1R-M5R, OCT3, VACHT, and ACHE; proinflammatory cytokines; and Ach concentration in the SA group were significantly higher than those in the non-SA group. Furthermore, most NNCS components positively correlated with non-type (T) 2 inflammatory profiles, such as sputum neutrophils, IL8, and IL1B. In addition, the mRNA levels of sputum M2R, M3R, M4R, M5R, and VACHT were independently associated with an increased risk of moderate-to-severe asthma exacerbations. CONCLUSION: This study indicated that the NNCS was significantly activated in SA, leading to elevated Ach and was associated with clinical features, non-T2 inflammation, and future exacerbations of asthma, highlighting the potential role of the NNCS in the pathogenesis of SA. CLINICAL TRIAL REGISTRATION: ChiCTR-OOC-16009529 (http://www.chictr.org.cn).

Emerging role of tumor suppressing microRNAs as therapeutics in managing non-small cell lung cancer.

Lung cancer (LC) is the second leading cause of death across the globe after breast cancer. There are two types of LC viz. small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC accounts for approximately 85% of all LC cases. NSCLC affects smokers and people who do not smoke and mainly arises in bronchi and peripheral lungs tissue. LC is often characterized by the alterations of key genes such as EGFR, Wnt/ß-catenin signaling, ALK, MET, K-Ras and p53 and downstream signaling pathways associated with tumor growth, differentiation, and survival. Numerous miRNAs have been discovered as a result of advances in biotechnology to treat LC. Various miRNAs those have been identified to treat LC include mir-Let7, mir-34a, mir-134, mir-16-1, mir-320a, mir-148a, mir-125a-5p, mir-497, mir-29, mir-133a, and mir-29a-3p. These miRNAs target various signaling pathways that are involved in pathogenesis of LC. However, due to rapid RNAse degradation, quick clearance, and heat instability, associated with necked miRNA leads to less effective therapeutic effect against LC. Therefore, to overcome these challenges nanocarrier loaded with miRNAs have been reported. They have been found promising because they have the capacity to target the tumor as well as they can penetrate the tumors deep due to nanometer size. Some of the clinical trials have been performed using miR-34a and let-7 for the treatment of LC. In the present manuscript we highlight the role miRNAs as well as their nanoparticle in tumor suppression.

The application of nanoparticles as advanced drug delivery systems in Attenuating COPD.

Chronic Obstructive Pulmonary Disease (COPD) is a dilapidating condition which is characterized by inflammation, an excess in free radical generation and airway obstruction. Currently, the drugs commercially available for the management of COPD pose several limitations such as systemic adverse effects, including bone density loss and an increased risk of developing pneumonia. Moreover, another limitation includes the need for regular and frequent dosing regimens; which can affect the adherence to the therapy. Furthermore, these current treatments provide symptomatic relief; however, they cannot stop the progression of COPD. Comparatively, nanoparticles (NPs) provide great therapeutic potential to treat COPD due to their high specificity, biocompatibility, and higher bioavailability. Furthermore, the NP-based drug delivery systems involve less frequent dosing requirements and in smaller doses which assist in minimizing side effects. In this review, the benefits and limitations of conventional therapies are explored, while providing an in-depth insight on advanced applications of NP-based systems in the treatment of COPD.

Clinical Subtypes of Neutrophilic Asthma: A Cluster Analysis From Australasian Severe Asthma Network.

BACKGROUND: Clinical heterogeneity may exist within asthma subtypes defined by inflammatory markers. However, the heterogeneity of neutrophilic asthma (NA) remains largely unexplored. OBJECTIVE: To explore potential clusters and the stability of NA. METHODS: Participants with NA from the Australasian Severe Asthma Network underwent a multidimensional assessment. They were then asked to participate in a 12-month longitudinal cohort study. We explored potential clusters using a hierarchical cluster analysis and validated the differential future risk of asthma exacerbations in the identified clusters. A decision tree analysis was developed to predict cluster assignments. Finally, the stability of prespecified clusters was examined within 1 month. RESULTS: Three clusters were identified in 149 patients with NA. Cluster 1 (n = 99; 66.4%) was characterized by female-predominant nonsmokers with well-controlled NA, cluster 2 (n = 16; 10.7%) by individuals with comorbid anxiety/depressive symptoms with poorly controlled NA, and cluster 3 by older male smokers with late-onset NA. Cluster 2 had a greater proportion of participants with severe exacerbations (P = .005), hospitalization (P = .010), and unscheduled visits (P = .013) and a higher number of emergency room visits (P = .039) than that of the other two clusters. The decision tree assigned 92.6% of participants correctly. Most participants (87.5%; n = 7) in cluster 2 had a stable NA phenotype, whereas participants of clusters 1 and 3 had variable phenotypes. CONCLUSIONS: We identified three clinical clusters of NA, in which cluster 2 represents an uncontrolled and stable NA subtype with an elevated risk of exacerbations. These findings have clinical implications for the management of NA.

Zerumbone liquid crystalline nanoparticles protect against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro.

The purpose of this study was to evaluate the potential of zerumbone-loaded liquid crystalline nanoparticles (ZER-LCNs) in the protection of broncho-epithelial cells and alveolar macrophages against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro. The effect of the treatment of ZER-LCNs on in vitro cell models of cigarette smoke extract (CSE)-treated mouse RAW264.7 and human BCi-NS1.1 basal epithelial cell lines was evaluated for their anti-inflammatory, antioxidant and anti-senescence activities using colorimetric and fluorescence-based assays, fluorescence imaging, RT-qPCR and proteome profiler kit. The ZER-LCNs successfully reduced the expression of pro-inflammatory markers including Il-6, Il-1ß and Tnf-α, as well as the production of nitric oxide in RAW 264.7 cells. Additionally, ZER-LCNs successfully inhibited oxidative stress through reduction of reactive oxygen species (ROS) levels and regulation of genes, namely GPX2 and GCLC in BCi-NS1.1 cells. Anti-senescence activity of ZER-LCNs was also observed in BCi-NS1.1 cells, with significant reductions in the expression of SIRT1, CDKN1A and CDKN2A. This study demonstrates strong in vitro anti-inflammatory, antioxidative and anti-senescence activities of ZER-LCNs paving the path for this formulation to be translated into a promising therapeutic agent for chronic respiratory inflammatory conditions including COPD and asthma.

Advances in nano-based drug delivery systems for the management of cytokine influx-mediated inflammation in lung diseases.

Asthma, lung cancer, cystic fibrosis, tuberculosis, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and COVID-19 are few examples of inflammatory lung conditions that cause cytokine release syndrome. It can initiate a widespread inflammatory response and may activate several inflammatory pathways that cause multiple organ failures leading to increased number of deaths and increased prevalence rates around the world. Nanotechnology-based therapeutic modalities such as nanoparticles, liposomes, nanosuspension, monoclonal antibodies, and vaccines can be used in the effective treatment of inflammatory lung diseases at both cellular and molecular levels. This would also help significantly in the reduction of patient mortality. Therefore, nanotechnology could be a potent platform for repurposing current medications in the treatment of inflammatory lung diseases. The aim and approach of this article are to highlight the clinical manifestations of cytokine storm in inflammatory lung diseases along with the advances and potential applications of nanotechnology-based therapeutics in the management of cytokine storm. Further in-depth studies are required to understand the molecular pathophysiology, and how nanotechnology-based therapeutics can help to effectively combat this problem.

Third-Hand Exposure to E-Cigarette Vapour Induces Pulmonary Effects in Mice.

In the last decade, e-cigarette usage has increased, with an estimated 82 million e-cigarette users globally. This is, in part, due to the common opinion that they are "healthier" than tobacco cigarettes or simply "water vapour". Third-hand e-vapour exposure is the chemical residue left behind from e-cigarette aerosols, which is of concern due to its invisible nature, especially among young children. However, there is limited information surrounding third-hand e-vapour exposure. This study aimed to investigate the pulmonary effects of sub-chronic third-hand e-vapour exposure in a murine model. BALB/c mice (4 weeks of age) were exposed to a towel containing nicotine free (0 mg) e-vapour, nicotine (18 mg) e-vapour, or no e-vapour (sham) and replaced daily for 4 weeks. At the endpoint, lung function was assessed, and bronchoalveolar lavage fluid and lungs were collected to measure inflammation and fibrosis. Mice exposed to third-hand e-vapour without nicotine had alveolar enlargement compared to sham exposed controls. Mice exposed to third-hand e-vapour with nicotine had reduced bronchial responsiveness to provocation, increased epithelial thickening in large airways, increased epithelial layers in small airways, alveolar enlargement, and increased small airway collagen deposition, compared to sham exposed controls. In conclusion, our study shows that third-hand e-vapour exposure, particularly in the presence of nicotine, negatively affects the lung health of mice and highlights the need for greater public awareness surrounding the dangers of third-hand exposure to e-cigarette vapour.

Effect of E-Vaping on Kidney Health in Mice Consuming a High-Fat Diet.

High-fat diet (HFD) consumption and tobacco smoking are risk factors for chronic kidney disease. E-cigarettes have gained significant popularity among younger populations worldwide, especially among overweight individuals. It is unclear whether vaping interacts with HFD consumption to impact renal health. In this study, Balb/c mice (male, 7 weeks old) were fed a pellet HFD (43% fat, 20 kJ/g) for 16 weeks when exposed to nicotine or nicotine-free e-vapour from weeks 11 to 16. While HFD alone increased collagen Ia and IV depositions, it did not cause significant oxidative stress and inflammatory responses in the kidney itself. On the other hand, e-vapour exposure alone increased oxidative stress and damaged DNA and mitochondrial oxidative phosphorylation complexes without significant impact on fibrotic markers. However, the combination of nicotine e-vapour and HFD increased inflammatory responses, oxidative stress-induced DNA injury, and pro-fibrotic markers, suggesting accelerated development of renal pathology. Nicotine-free e-vapour exposure and HFD consumption suppressed the production of mitochondrial OXPHOS complexes and extracellular matrix protein deposition, which may cause structural instability that can interrupt normal kidney function in the future. In conclusion, our study demonstrated that a HFD combined with e-cigarette vapour exposure, especially when containing nicotine, can increase susceptibility to kidney disease.

Effectiveness of Pulmonary Rehabilitation for Chronic Obstructive Pulmonary Disease Therapy: Focusing on Traditional Medical Practices.

Chronic obstructive pulmonary disease (COPD) is a complex and serious disease that is characterized by dyspnea, fatigue, decreased exercise tolerance, peripheral muscle dysfunction, and mood disorders. These manifestations are successfully treated with pulmonary rehabilitation, a comprehensive intervention and holistic approach designed to improve the physical and psychological condition of people with COPD. Exercise is a big component of pulmonary rehabilitation programs, but the efficacy of non-traditional forms of exercise as used in alternative medicine is poorly understood. Here, we aim to address this gap in knowledge and summarize the clinical evidence for the use of traditional exercise regimens in the pulmonary rehabilitation of COPD patients.

Effects of e-vapour and high-fat diet on the immunohistochemical staining of nicotinic acetylcholine receptors, apoptosis, microglia and astrocytes in the adult male mouse hippocampus.

The use of e-cigarettes/e-vapour, and the consumption of a high-fat diet (HFD), are two popular lifestyle choices associated with alterations in the hippocampus. This study, using a mouse model, investigated the effects of exposure to e-vapour (± nicotine) and HFD (43% fat) consumption, on the expression of nicotinic acetylcholine receptor (nAChR) subunits α3, α4, α7 and ß2, apoptosis markers caspase-3 and TUNEL, microglial marker Iba-1, and astrocyte marker GFAP, in hippocampal subregions of dentate gyrus (DG) and cornu ammonis (CA) 1-3. The major findings included: (1) HFD alone had minimal effect with no consistent pattern or interaction between the markers, (2) E-vapour (± nicotine) predominantly affected the CA2 subregion, decreasing α7 and ß2 nAChR subunits and Iba-1, (3) Nicotine e-vapour increased TUNEL across all subregions, and (4) HFD, in the presence of nicotine-free e-vapour, decreased caspase-3 and increased TUNEL across all regions, and decreased Iba-1 in the CA subregions, while HFD and nicotine-containing e-vapour, subregion specifically affected the α3, α4 and α7 nAChR subunits, with a protective effect against change in GFAP in the DG and Iba-1 in the CA1 and CA3. These findings highlight that e-vapour itself alters nAChRs, particularly in the CA2 subregion, associated with a decrease in neuroinflammatory response (Iba-1) across the whole hippocampus, and the addition of nicotine increases cell apoptosis across the whole hippocampus. HFD alone was not detrimental in our model, but in the presence of nicotine-free e-vapour, it differentially affected apoptosis, while the addition of nicotine increased nAChR subunits.

E-Cigarette Vapour Alters High-Fat Diet-Induced Systemic Inflammatory Responses but Has No Effect on High-Fat Diet-Induced Changes in Gut Microbiota.

BACKGROUND: The gut microbiome, which can be altered by different diets or smoking, has been implicated in the pathogenesis of lung conditions. E-cigarette vaping is now recognised to have detrimental health effects, with several of these being similar to cigarette smoking. However, whether e-cigarettes can alter high-fat diet (HFD)-induced systemic effects and gut microbiota is unknown. In this study, we investigated the effects of HFD in the absence/presence of e-cigarette exposure on systemic inflammation, lipid metabolic markers, and the gut microbiome. METHODS: Mice were fed a HFD (or chow) in the absence/presence of e-vapour exposure (±nicotine) and serum inflammation, lipid levels, and microbial diversity were assessed. RESULTS: HFD increased the circulating levels of both triglycerides and non-esterified fatty acids, which were significantly reduced by e-vapour exposure in HFD-fed mice. Serum TNF-α was increased by HFD consumption or e-vapour. HFD had a significant effect on microbial diversity, but there were no additional effects of e-vapour exposure. CONCLUSIONS: This study highlights both similarities and differences in how the body responds to e-cigarette vapours, and it is therefore likely that the long-term sequelae of e-cigarette vapour exposure/vaping might not involve the significant alteration of the gut microbiome.

E-Cigarette Aerosol Condensate Leads to Impaired Coronary Endothelial Cell Health and Restricted Angiogenesis.

Cardiovascular disease (CVD) is a leading cause of mortality worldwide, with cigarette smoking being a major preventable risk factor. Smoking cessation can be difficult due to the addictive nature of nicotine and the withdrawal symptoms following cessation. Electronic cigarettes (e-Cigs) have emerged as an alternative smoking cessation device, which has been increasingly used by non-smokers; however, the cardiovascular effects surrounding the use of e-Cigs remains unclear. This study aimed to investigate the effects of e-Cig aerosol condensate (EAC) (0 mg and 18 mg nicotine) in vitro on human coronary artery endothelial cells (HCAEC) and in vivo on the cardiovascular system using a mouse model of 'e-vaping'. In vitro results show a decrease in cell viability of HCAEC when exposed to EAC either directly or after exposure to conditioned lung cell media (p < 0.05 vs. control). Reactive oxygen species were increased in HCAEC when exposed to EAC directly or after exposure to conditioned lung cell media (p < 0.0001 vs. control). ICAM-1 protein expression levels were increased after exposure to conditioned lung cell media (18 mg vs. control, p < 0.01). Ex vivo results show an increase in the mRNA levels of anti-angiogenic marker, FKBPL (p < 0.05 vs. sham), and endothelial cell adhesion molecule involved in barrier function, ICAM-1 (p < 0.05 vs. sham) in murine hearts following exposure to electronic cigarette aerosol treatment containing a higher amount of nicotine. Immunohistochemistry also revealed an upregulation of FKBPL and ICAM-1 protein expression levels. This study showed that despite e-Cigs being widely used for tobacco smoking cessation, these can negatively impact endothelial cell health with a potential to lead to the development of cardiovascular disease.