title: Differences in cardiovascular toxicities associated with cigarette smoking and snuff use revealed using novel zebrafish models.
abstract: 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.
authors.affiliation: Division of Drug Research, Department of Medical and Health Sciences, Linköping University, 581 85 Linköping, Sweden.
authors.forename: Maggie
authors.initials: M
authors.lastname: Folkesson
authors.affiliation: Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, 581 85 Linköping, Sweden.
authors.forename: Natalia
authors.initials: N
authors.lastname: Sadowska
authors.affiliation: Division of Drug Research, Department of Medical and Health Sciences, Linköping University, 581 85 Linköping, Sweden.
authors.forename: Svante
authors.initials: S
authors.lastname: Vikingsson
authors.affiliation: Division of Applied Thermodynamics and Fluid Mechanics, Department of Management and Engineering, Linköping University, 581 83 Linköping, Sweden.
authors.forename: Matts
authors.initials: M
authors.lastname: Karlsson
authors.affiliation: Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, 581 85 Linköping, Sweden.
authors.forename: Carl-Johan
authors.initials: CJ
authors.lastname: Carlhäll
authors.affiliation: Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, 581 85 Linköping, Sweden.
authors.forename: Toste
authors.initials: T
authors.lastname: Länne
authors.affiliation: Division of Drug Research, Department of Medical and Health Sciences, Linköping University, 581 85 Linköping, Sweden.
authors.forename: Dick
authors.initials: D
authors.lastname: Wågsäter
authors.affiliation: Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, 581 85 Linköping, Sweden lasse.jensen@liu.se.
authors.forename: Lasse
authors.identifier: http://orcid.org/0000-0003-2338-357X
authors.initials: L
authors.lastname: Jensen
keywords: Aneurysm; Aorta; Cardiovascular; Snuff; Tobacco; Zebrafish