Electronic cigarettes cause alteration in cardiac structure and function in diet-induced obese mice

Abstract

In spite of the widespread use of electronic cigarettes, also known as e-cigarettes, and the proposed adverse cardiac effects of nicotine, the detrimental effects of e-cigarettes on the heart are not well known. This study examines the detrimental effects of e-cigarettes with nicotine at doses that yield circulating nicotine and cotinine in the ranges similar to the levels found in habitual smokers, and a high fat diet (HFD) on cardiac structure and function in a commonly used model of diet-induced obesity (DIO). C57BL/6J mice on an HFD were exposed to e-cigarette in the presence (2.4% nicotine) or absence (0% nicotine) of nicotine and saline aerosol for 12 weeks. Echocardiographic data demonstrated a decrease in left ventricular (LV) fractional shortening, LV ejection fraction, and velocity of circumferential fiber shortening (VCF) in mice treated with e-cigarette (2.4% nicotine) compared to e-cigarette (0% nicotine) or saline exposed mice. Cardiomyocytes (CMs) of mice treated with ecigarette (2.4% nicotine) exhibited LV abnormalities, including lipid accumulation (ventricular steatosis), myofibrillar derangement and destruction, and mitochondrial hypertrophy, as revealed by transmission electron microscopy. The detrimental effects of e-cigarettes (2.4% nicotine) on cardiac structure and function was accompanied by increased oxidative stress, plasma free fatty acid levels, CM apoptosis, and inactivation of AMP-activated protein kinase and activation of its downstream target, acetyl-CoA-carboxylase. Our results indicate profound adverse effects of e-cigarettes (2.4% nicotine) on the heart in obese mice and raise questions about the safety of the nicotine e-cigarettes use.

EHBP1, TUBB, and WWOX SNPs, Gene-Gene and Gene-Environment Interactions on Coronary Artery Disease and Ischemic Stroke

“…It is mediated through the ABCA1/apolipoprotein (Apo) A1 pathway, and it binds to a series of potential ligands of proline-rich PPxY motifs and other kinds of cell proteins. It is also involved in a variety of other pathways, including cholesterol homeostasis, fatty acid biosynthesis and triglyceride (TG) metabolism ( Iatan et al, 2014 ; Hasan et al, 2020 ), GWAS indicated that there was an association between the fasting lipid profile of 1,087 participants in an offspring cohort (mean age 47 years, 52% female) and WWOX . The correlation between the WWOX rs2222896AA genotype and LDL-C was two times that of the rs2222896AG or rs2222896 GG genotypes ( Johannsen et al, 2018 ).…”

E-cigarette aerosol exacerbates cardiovascular oxidative stress in mice with an inactive aldehyde dehydrogenase 2 enzyme

“…E-cigarette use also elevates oxidized low-density lipoprotein, a marker of oxidative stress, 1.5-fold in humans when compared to non-e-cigarette, non-tobacco users [ 37 ]. Additionally, e-cigarette aerosol can trigger lipid peroxidation which form endogenous aldehydes including 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) [ 26 , 38 ]. As 4-HNE can inhibit ALDH2 enzymatic activity, this can further drive increases in oxidative stress levels from e-cigarette exposures by limiting acetaldehyde metabolism [ 8 ].…”

Use of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes to Predict the Cardiotoxicity Potential of Next Generation Nicotine Products

“…Reduced cardiovascular effects have also been reported in longer term in vivo and clinical studies with people switching from cigarettes to EVPs, including substantial reductions in biomarkers of exposure to toxicants (including cardiovascular toxicants) in adult smokers who switch from combustible cigarettes to EVP (O'Connell et al, 2016;National Academies of Sciences et al, 2018;Hasan et al, 2020;Abouassali et al, 2021). Moreover, a recent British Heart Foundation funded clinical study found that adult smokers who switched to EVP for 1 month showed favourable improvements in cardiovascular endpoints with significant improvements in endothelial function, arterial stiffness and systolic blood pressure compared with continuing smoking (George et al, 2019).…”