Cardiac development in zebrafish and human embryonic stem cells is inhibited by exposure to tobacco cigarettes and e-cigarettes

PLoS One. 2015 May 15;10(5):e0126259. doi: 10.1371/journal.pone.0126259. eCollection 2015.


Background: Maternal smoking is a risk factor for low birth weight and other adverse developmental outcomes.

Objective: We sought to determine the impact of standard tobacco cigarettes and e-cigarettes on heart development in vitro and in vivo.

Methods: Zebrafish (Danio rerio) were used to assess developmental effects in vivo and cardiac differentiation of human embryonic stem cells (hESCs) was used as a model for in vitro cardiac development.

Results: In zebrafish, exposure to both types of cigarettes results in broad, dose-dependent developmental defects coupled with severe heart malformation, pericardial edema and reduced heart function. Tobacco cigarettes are more toxic than e-cigarettes at comparable nicotine concentrations. During cardiac differentiation of hESCs, tobacco smoke exposure results in a delayed transition through mesoderm. Both types of cigarettes decrease expression of cardiac transcription factors in cardiac progenitor cells, suggesting a persistent delay in differentiation. In definitive human cardiomyocytes, both e-cigarette- and tobacco cigarette-treated samples showed reduced expression of sarcomeric genes such as MLC2v and MYL6. Furthermore, tobacco cigarette-treated samples had delayed onset of beating and showed low levels and aberrant localization of N-cadherin, reduced myofilament content with significantly reduced sarcomere length, and increased expression of the immature cardiac marker smooth muscle alpha-actin.

Conclusion: These data indicate a negative effect of both tobacco cigarettes and e-cigarettes on heart development in vitro and in vivo. Tobacco cigarettes are more toxic than E-cigarettes and exhibit a broader spectrum of cardiac developmental defects.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Embryonic Development / drug effects
  • Embryonic Stem Cells / drug effects*
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Heart / drug effects
  • Heart / embryology*
  • Heart / growth & development
  • Humans
  • Polymerase Chain Reaction
  • Smoking / adverse effects*
  • Zebrafish / embryology