title: Fetal origins of adult cardiac disease: a novel approach to prevent fetal growth restriction induced cardiac dysfunction using insulin like growth factor.
abstract: BACKGROUND
  Fetal growth restriction (FGR) is a risk factor for adult cardiovascular disease. Intraplacental gene transfer of human insulin-like growth factor-1 (IGF-1) corrects birth weight in our mouse model of FGR. This study addresses long term effects of FGR on cardiac function and the potential preventive effect of IGF-1.
  
  
  METHODS
  Laparotomy was performed on pregnant C57BL/6J mice at embryonic day 18 and pups were divided into three groups: Sham operated; FGR (induced by mesenteric uterine artery ligation); treatment (intraplacental injection of IGF-1 after uterine artery ligation). Pups were followed until 32 wk of life. Transthoracic echocardiography was performed starting at 12 wk.
  
  
  RESULTS
  Systolic cardiac function was significantly impaired in the FGR group with reduced fractional shortening compared with sham and treatment group starting at week 12 of life (20 ± 4 vs. 31 ± 5 vs. 32 ± 5, respectively, n = 12 for each group; P < 0.001) with no difference between the sham and treatment groups.
  
  
  CONCLUSIONS
  Intraplacental gene transfer of IGF-1 prevents FGR induced cardiac dysfunction. This suggests that in utero therapy may positively impact cardiac remodeling and prevent adult cardiovascular disease.
authors.affiliation: Cincinnati Children's Hospital Heart Institute, Cincinnati, Ohio.
authors.forename: Tarek
authors.initials: T
authors.lastname: Alsaied
authors.affiliation: Colorado Fetal Care Center, Division of Pediatric General Thoracic and Fetal Surgery, Children's Hospital of Colorado, Denver, Colorado.
authors.forename: Khaled
authors.initials: K
authors.lastname: Omar
authors.affiliation: Cincinnati Children's Hospital Heart Institute, Cincinnati, Ohio.
authors.forename: Jeanne F
authors.initials: JF
authors.lastname: James
authors.affiliation: Cincinnati Children's Hospital Heart Institute, Cincinnati, Ohio.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Hinton
authors.affiliation: Colorado Fetal Care Center, Division of Pediatric General Thoracic and Fetal Surgery, Children's Hospital of Colorado, Denver, Colorado.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Crombleholme
authors.affiliation: Center for Molecular Fetal Therapy, Cincinnati Children's Hospital, Cincinnati, Ohio.|Department of General and Thoracic Pediatric Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Mounira
authors.initials: M
authors.lastname: Habli
mesh_terms: D000818:Animals; D005260:Female; D005317:Fetal Growth Retardation; D006331:Heart Diseases / Q000209:etiology* / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D012727:Sex Characteristics
chemical_list: D007334:Insulin-Like Growth Factor I