title: Cardiac development in zebrafish and human embryonic stem cells is inhibited by exposure to tobacco cigarettes and e-cigarettes.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, Washington, United States of America; Center for Cardiovascular Biology, University of Washington School of Medicine, Seattle, Washington, United States of America; Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Palpant
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, Washington, United States of America; Center for Cardiovascular Biology, University of Washington School of Medicine, Seattle, Washington, United States of America; Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Hofsteen
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, Washington, United States of America; Center for Cardiovascular Biology, University of Washington School of Medicine, Seattle, Washington, United States of America; Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.
authors.forename: Lil
authors.initials: L
authors.lastname: Pabon
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, Washington, United States of America; Center for Cardiovascular Biology, University of Washington School of Medicine, Seattle, Washington, United States of America; Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.
authors.forename: Hans
authors.initials: H
authors.lastname: Reinecke
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, Washington, United States of America; Department of Bioengineering, University of Washington School of Medicine, Seattle, Washington, United States of America; Department of Medicine/Cardiology, University of Washington School of Medicine, Seattle, Washington, United States of America; Center for Cardiovascular Biology, University of Washington School of Medicine, Seattle, Washington, United States of America; Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Murry
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000187:drug effects*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006321:Heart / Q000187:drug effects / Q000196:embryology* / Q000254:growth & development; D006801:Humans; D016133:Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects*; D015027:Zebrafish / Q000196:embryology