Potentially reduced exposure cigarettes accelerate atherosclerosis: Evidence for the role of nicotine

Daniel F. Catanzaro, Ying Zhou, Rong Chen, Fangmin Yu, Sarah E. Catanzaro, Mariana S. De Lorenzo, Kotha Subbaramaiah, Xi Kathy Zhou, Domenico Pratico, Andrew J. Dannenberg, Babette B. Weksler

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


The tobacco industry markets potentially reduced exposure products (PREPs) as less harmful or addictive alternatives to conventional cigarettes. This study compared the effects of mainstream smoke from Quest, Eclipse, and 2R4F reference cigarettes on the development of atherosclerosis in apolipoprotein E-deficient (apoE -/-) mice. Mice were exposed to smoke from four cigarette types for 12 weeks beginning at age of 12 weeks, and in a separate study for 8 weeks, beginning at age of 8 weeks. In both studies, mice exposed to smoke from high-nicotine, high-tar Quest 1, and 2R4F cigarettes developed greater areas of lipid-rich aortic lesions than did non-smoking controls. Exposure to smoke from the lower-nicotine products, Eclipse, and Quest 3, was associated with smaller lesion areas, but animals exposed to smoke from all of the tested types of cigarette had larger lesions than did control animals not exposed to smoke. Urinary levels of isoprostane F2 alpha VI, increased proportionally to cigarette nicotine yield, whereas induction of pulmonary cytochrome P4501A1 was proportional to tar yield. Lesion area was associated with both nicotine and tar yields, although in multiple regression analysis only nicotine was a significant predictor of lesion area. Smoke exposure did not alter systolic blood pressure (SBP), heart rate (HR), blood cholesterol, or leukocyte count. Taken together, these observations suggest that smoking may accelerate atherosclerosis by increasing oxidative stress mediated at least in part via the actions of nicotine.

Original languageEnglish (US)
Pages (from-to)192-201
Number of pages10
JournalCardiovascular Toxicology
Issue number3
StatePublished - Sep 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Toxicology
  • Cardiology and Cardiovascular Medicine


  • Complete blood count
  • Cytochrome P450
  • Isoprostane
  • Oxidative stress
  • Sympathetic nervous system


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