title: Mammalian fetal cardiac regeneration after myocardial infarction is associated with differential gene expression compared with the adult.
abstract: BACKGROUND
  In adults, myocardial infarction (MI) results in a brisk inflammatory response, myocardium loss, and scar formation. We have recently reported the first mammalian large-animal model of cardiac regeneration after MI in fetal sheep. We hypothesize that the ability of the fetus to regenerate functional myocardium after MI is owing to differential gene expression regulating the response to MI in the fetus compared with the adult.
  
  
  METHODS
  Myocardial infarction was created in adult (n=4) or early gestation fetal (n=4) sheep. Tissue was harvested after 3 or 30 days, and RNA was extracted for microarray, followed by principal component analysis and global gene expression analysis for the following gene ontology terms: response to wounding, inflammatory response, extracellular matrix, cell cycle, cell migration, cell proliferation, and apoptosis.
  
  
  RESULTS
  Principal component analysis demonstrated that the global gene expression pattern in adult infarcts was distinctly different from the uninfarcted region at 3 days and remained different at 30 days after MI. In contrast, gene expression in the fetal infarct was different from the uninfarcted region at 3 days, but by 30 days it returned to a baseline expression pattern similar to the uninfarcted region. Three days after MI there was an increase in the expression of genes related to all gene ontology terms in fetal and adult infarcts, but this increase was much more pronounced in adults. By 30 days, the fetal gene expression returned to baseline, whereas in the adult it remained significantly elevated.
  
  
  CONCLUSIONS
  These data demonstrate that the global gene expression pattern is dramatically different in the fetal regenerative response to MI compared with the adult response and may partly be responsible for the regeneration.
authors.affiliation: Department of Surgery, Nemours Children Hospital, Orlando, Florida.
authors.forename: Carlos
authors.initials: C
authors.lastname: Zgheib
authors.affiliation: The Department of Surgery and the Gorman Cardiovascular Research Group, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Myron W
authors.initials: MW
authors.lastname: Allukian
authors.affiliation: Department of Surgery, Nemours Children Hospital, Orlando, Florida.
authors.forename: Junwang
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Surgery, Nemours Children Hospital, Orlando, Florida.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Morris
authors.affiliation: The Department of Surgery and the Gorman Cardiovascular Research Group, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Caskey
authors.affiliation: The Department of Surgery and the Gorman Cardiovascular Research Group, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Herdrich
authors.affiliation: Department of Surgery, Nemours Children Hospital, Orlando, Florida.
authors.forename: Junyi
authors.initials: J
authors.lastname: Hu
authors.affiliation: The Department of Surgery and the Gorman Cardiovascular Research Group, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. Electronic address: robert.gorman@uphs.upenn.edu.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Gorman
authors.affiliation: The Department of Surgery and the Gorman Cardiovascular Research Group, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gorman
authors.affiliation: Department of Surgery, Nemours Children Hospital, Orlando, Florida.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Liechty
mesh_terms: D000328:Adult; D000367:Age Factors; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005318:Fetal Heart / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000502:physiology; D006801:Humans; D009203:Myocardial Infarction / Q000196:embryology* / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D011270:Pregnancy, Animal; D012313:RNA / Q000235:genetics; D011897:Random Allocation; D012038:Regeneration / Q000502:physiology*; D012680:Sensitivity and Specificity; D012756:Sheep; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D012313:RNA