Cardiovascular Effects of Exposure to Tobacco Products and Harmful Constituents

Smoking is the leading cause of preventable death worldwide and is responsible for roughly 480,000 annual deaths in U.S. alone. And while cigarette smoking increases the risk of several chronic diseases, such as cancer and respiratory disease, cardiovascular deaths account for nearly half of overall smoking-related mortality. Moreover, 80-85% of the non-cancer health risk associated with smoking (i.e., cardiovascular and pulmonary disease risk) is thought to be the result of a single compound called acrolein. However, new and emerging tobacco products, such as electronic cigarettes (e-cigs) and snus, have quickly gained popularity.  The use of e-cigs in particular is increasing rapidly around the world, but little is known about the actual health effects of these tobacco products. Unlike traditional cigarettes, e-cigs do not rely on tobacco burning for the delivery of nicotine and thus do not generate smoke.  E-cigs generate an aerosol (vapor), however, that alters indoor air quality and contains toxic aldehydes: formaldehyde and acrolein. Thus, we investigated the cardiovascular toxicity of tobacco products using both acute and chronic exposures. For this, mice were exposed to e-cig aerosol, tobacco smoke, smokeless tobacco, nicotine, or acrolein. Urinary metabolites of exposure-derived nicotine and aldehydes were measured to know the specific levels of nicotine and aldehyde with different tobacco exposures. Following acute and chronic exposures, important cardiovascular risk factors were measured including platelet-leukocyte aggregation (blood clot), insulin resistance (pre-diabetes), circulating immune and endothelial progenitor cells (immunity and vascular repair, respectively) and atherogenesis (blood vessel plaque buildup). These effects were compared with the effects of nicotine- or aldehyde-only exposure to understand if either constituent was sufficiently toxic. Similar to mainstream cigarette smoke exposure (and consistent with published data), e-cig or smokeless tobacco exposure also increased atherosclerosis in mice.  Somewhat surprising, however, was the discovery that either nicotine or acrolein alone (at levels present in smokeless and mainstream smoke, respectively) increased atherosclerosis in mice indicating that multiple constituents have potential to cause cardiovascular disease. Similarly, acute exposure to either cigarette smoke or aerosol e-cig depressed levels of blood cells important in disease immunity and vascular repair implicating these changes as potential mechanisms whereby new tobacco products accelerated atherosclerosis.