Differences in cardiovascular toxicities associated with cigarette smoking and snuff use revealed using novel zebrafish models

Tobacco use is strongly associated with cardiovascular disease and the only avoidable risk factor associated with development of aortic aneurysm. While smoking is the most common form of tobacco use, snuff and other oral tobacco products are gaining popularity, but research on potentially toxic effects of oral tobacco use has not kept pace with the increase in its use. Here, we demonstrate that cigarette smoke and snuff extracts are highly toxic to developing zebrafish embryos. Exposure to such extracts led to a palette of toxic effects including early embryonic mortality, developmental delay, cerebral hemorrhages, defects in lymphatics development and ventricular function, and aneurysm development. Both cigarette smoke and snuff were more toxic than pure nicotine, indicating that other compounds in these products are also associated with toxicity. While some toxicities were found following exposure to both types of tobacco product, other toxicities, including developmental delay and aneurysm development, were specifically observed in the snuff extract group, whereas cerebral hemorrhages were only found in the group exposed to cigarette smoke extract. These findings deepen our understanding of the pathogenic effects of cigarette smoking and snuff use on the cardiovascular system and illustrate the benefits of using zebrafish to study mechanisms involved in aneurysm development.The Jensen laboratory is supported by grants from Svenska Sallskapet for Medicinsk Forskning [grant F14-0021], Linkopings Universitet, Eva och Oscar Ahrens Stiftelse, Ollie och Elof Ericssons Stiftelse, Carmen och Bertil Ragners Stiftelse, Gosta Fraenkels Stiftelse, Ake Wibergs Stiftelse, Lions Forskningsfond, Karin Sandbergs Stiftelse, Cancerfonden, Karolinska Institutet's Stiftelser och Fonder and Vetenskapsradet [grant 2015-06271].