Abstract 19357: Mechanisms of Tobacco Products Induced Exacerbation of Atherosclerosis
Smoking has been shown to exacerbate atherosclerosis; however it is unclear which constituents of tobacco smoke/products aggravate atherogenesis. Smokeless tobacco (ST) and mainstream cigarette smoke (MCS) contain thousands of chemicals and therefore, it has not been possible to identify which of these chemicals cause cardiovascular injury. In this study we examined the effect of tobacco products and their constituents on atherogenesis. Exposure of 8 week old male apoE-KO mice (maintained on Western diet) to MCS (6h/day, 7days/week for 12 weeks; n=15/group) increased the plasma cholesterol by 21% (P<0.05) and aortic lesion formation by >1.5 fold (P<0.05) whereas plasma cholesterol levels and lesion formation in MCS-exposed female mice were comparable with air-exposed controls. Male mice exposed to inhaled acrolein (n=15; levels matched to the urinary metabolite of acrolein in MCS exposed mice), the most reactive and abundant aldehyde present in tobacco smoke, increased aortic lesion formation by >1.5-fold (P< 0.05) but did not affect plasma cholesterol levels. Inflammatory gene array showed that acrolein exposure induces CCL6 in the lungs. Exposure of mice (n=15-25/group) to ST products - snuff, snus or nicotine (matched to the levels of plasma nicotine in smokers) in drinking water for 12 weeks increased aortic atherosclerosis by 1.5-1.8 fold (P<0.05). This was accompanied by 20-25% increase in plasma cholesterol levels. Gene array of the livers of nicotine-exposed mice showed 3-fold induction of ApoB (P<0.05). Mass spectrometric analyses showed only traces of metals in tobacco extracts; and levels of metabolites of aldehydes, including acrolein, in mice exposed to ST were comparable with water-fed controls. Together, these data suggest that a) nicotine and acrolein are sufficient to exacerbate atherogenesis; b) acrolein and structurally related aldehydes present in cigarette smoke are mostly derived from the combustion of tobacco and could cause pulmonary inflammation; and c) nicotine in tobacco products induces apoB in the liver, which could increase plasma cholesterol and exacerbate atherosclerosis.
Author Disclosures: M.V. Malovichko: None. A. Agarwal: None. S.D. Sithu: None. I. Zeller: None. M. Winner: None. M.E. Smith: None. N.S. Wickramasinghe: None. A. Bhatnagar: None. D.J. Conklin: None. S. Srivastava: None.
- © 2016 by American Heart Association, Inc.