title: Activation of the mitogen-activated protein kinases and Akt in response to pulmonary artery banding in the fetal sheep heart is developmentally regulated.
abstract: BACKGROUND
  The postnatal heart responds to biomechanical stress with hypertrophy. The fetal heart may also undergo hyperplasia, but the percentage of mitotically active cardiomyocytes decreases throughout gestation. The signaling pathways controlling growth and proliferation in the fetal heart are poorly understood.
  
  
  OBJECTIVE
  To determine whether activation of the mitogen-activated protein kinases and Akt in the acute response to pressure loading in the fetal heart is developmentally regulated.
  
  
  METHODS
  Pulmonary artery banding (PAB) was performed in 100- or 128-day fetuses of twin gestation (n = 6 per group) for 6 h. One twin served as a control. Right ventricular (RV) and left ventricular (LV) mitogen-activated protein kinase, Akt, and cyclin D1 protein levels were determined by Western blot.
  
  
  RESULTS
  Within each gestational age group, hemodynamic and arterial blood gas values were similar between PAB and control fetuses. The total mitogen-activated protein kinase and Akt protein levels were unchanged by PAB at both gestational ages, as were active p38 and JNK levels. The RV levels of active ERK tended to decrease in 128-day PAB fetuses as compared with controls, and LV active ERK normalized to total ERK was significantly decreased. At gestational age (GA) 100 days, RV active ERK levels were significantly higher in PAB animals as compared with controls, with a trend towards increased active Akt levels. No differences were seen in the 100-day LV. The levels of the cell cycle promoter cyclin D1 were unchanged in all animals.
  
  
  CONCLUSIONS
  Pressure loading of the fetal sheep heart leads to developmentally regulated cell signaling profiles. ERK and possibly Akt may be important regulators of in vivo cardiomyocyte hyperplasia.
authors: Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
authors: Aaron K
authors: AK
authors: Olson
authors: Kristen N
authors: KN
authors: Protheroe
authors: Thomas D
authors: TD
authors: Scholz
authors: Jeffrey L
authors: JL
authors: Segar
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology; D019938:Cyclin D1 / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D005333:Fetus; D006321:Heart / Q000196:embryology* / Q000502:physiology; D006339:Heart Rate / Q000502:physiology; D006965:Hyperplasia; D015151:Immunoblotting; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D009929:Organ Size; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011651:Pulmonary Artery / Q000502:physiology / Q000601:surgery*; D011652:Pulmonary Circulation / Q000502:physiology; D012756:Sheep / Q000196:embryology* / Q000502:physiology; D014656:Vascular Surgical Procedures
chemical_list: D019938:Cyclin D1; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases