title: In utero and early life exposure to diesel exhaust air pollution increases adult susceptibility to heart failure in mice.
abstract: BACKGROUND
  Fine particulate air pollution (PM2.5) is a global health concern, as exposure to PM2.5 has consistently been found to be associated with increased cardiovascular morbidity and mortality. Although adult exposure to traffic related PM2.5, which is largely derived from diesel exhaust (DE), has been associated with increased cardiac hypertrophy, there are limited investigations into the potential effect of in utero and early life exposure on adult susceptibility to heart disease. In this study, we investigate the effect of in utero and early life exposure to DE on adult susceptibility to heart failure.
  
  
  METHODS
  Female C57BL/6 J mice were exposed to either filtered air (FA) or DE for 3 weeks (≈ 300 μg/m3 PM2.5 for 6 hours/day, 5 days/week) and then introduced to male breeders for timed matings. Female mice were exposed to either FA or DE throughout pregnancy and until offspring were 3 weeks of age. Offspring were then transferred to either FA or DE for an additional 8 weeks of exposure. At 12 weeks of age, male offspring underwent a baseline echocardiographic assessment, followed by a sham or transverse aortic constriction (TAC) surgery to induce pressure overload. Following sacrifice three weeks post surgery, ventricles were processed for histology to assess myocardial fibrosis and individual cardiomyocyte hypertrophy. mRNA from lung tissue was isolated to measure expression of inflammatory cytokines IL6 and TNFα.
  
  
  RESULTS
  We observed that mice exposed to DE during in utero and early life development have significantly increased susceptibility to cardiac hypertrophy, systolic failure, myocardial fibrosis, and pulmonary congestion following TAC surgery compared to FA control, or adult DE exposed mice. In utero and early life DE exposure also strongly modified the inflammatory cytokine response in the adult lung.
  
  
  CONCLUSIONS
  We conclude that exposure to diesel exhaust air pollution during in utero and early life development in mice increases adult susceptibility to heart failure. The results of this study may imply that the effects of air pollution on cardiovascular disease in human populations may be strongly mediated through a 'fetal origins' of adult disease pathway. Further investigations on this potential pathway of disease are warranted.
authors.forename: Chad S
authors.initials: CS
authors.lastname: Weldy
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Liu
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Chang
authors.forename: Ivan O
authors.initials: IO
authors.lastname: Medvedev
authors.forename: Julie R
authors.initials: JR
authors.lastname: Fox
authors.forename: Timothy V
authors.initials: TV
authors.lastname: Larson
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Chien
authors.affiliation: Division of Cardiology, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA. mtchin@u.washington.edu.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Chin
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004781:Environmental Exposure; D005260:Female; D006333:Heart Failure / Q000139:chemically induced*; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D001335:Vehicle Emissions
chemical_list: D016207:Cytokines; D001335:Vehicle Emissions