title: The impact of vascular endothelial growth factor and basic fibroblast growth factor on cardiac fibroblasts grown under altered gravity conditions.
abstract: BACKGROUND
  Myocardium is very sensitive to gravitational changes. During a spaceflight cardiovascular atrophy paired with rhythm problems and orthostatic intolerance can occur. The aim of this study was to investigate the impact of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) on cardiac fibroblasts (CF) grown under altered gravity conditions.
  
  
  METHODS
  We examined the influence of exposure to a Random Positioning Machine (RPM) on CF, derived from porcine hearts. We focused on growth, extracellular matrix protein (ECMP) synthesis and apoptosis.
  
  
  RESULTS
  When cultured on a RPM, CF began to form 3D spheroids within 24h, irrespective of growth factor treatment. Exposure to RPM induced an increased synthesis of ECMP and also resulted in elevated apoptosis in adherent CF as measured by terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick end labeling (TUNEL) analysis, 4',6-diamidino-2-phenylindole (DAPI) staining, and caspase-3 detection. bFGF and VEGF significantly decreased the amount of ECMP (collagen type I, III, chondroitin sulfate) in 1g and RPM cultures, and also significantly reduced the amount of apoptotic CF as well as caspase-3.
  
  
  CONCLUSIONS
  Altered gravity conditions on a RPM induced 3D growth, elevated ECMP synthesis and apoptosis in cardiac fibroblasts. Growth factor treatment attenuated programmed cell death and ECMP secretion.
authors.affiliation: Institute of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Ulbrich
authors.forename: Annekatrin
authors.initials: A
authors.lastname: Leder
authors.forename: Jessica
authors.initials: J
authors.lastname: Pietsch
authors.forename: Burkhard
authors.initials: B
authors.lastname: Flick
authors.forename: Markus
authors.initials: M
authors.lastname: Wehland
authors.forename: Daniela
authors.initials: D
authors.lastname: Grimm
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018470:Gravity, Altered; D009206:Myocardium / Q000166:cytology; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D002809:Chondroitin Sulfates; D053148:Caspase 3