title: c-Myc is required for proper coronary vascular formation via cell- and gene-specific signaling.
abstract: OBJECTIVE
  Although significant research has detailed angiogenesis during development and cancer, little is known about cardiac angiogenesis, yet it is critical for survival following pathological insult. The transcription factor c-Myc is a target of anticancer therapies because of its mitogenic and proangiogenic induction. In the current study, we investigate its role in cardiac angiogenesis in a cell-dependent and gene-specific context.
  
  
  RESULTS
  Angiogenesis assays using c-Myc-deficient cardiac endothelial cells and fibroblasts demonstrate that c-Myc is essential to vessel formation, and fibroblast-mediated vessel formation is dependent on c-Myc expression in fibroblasts. Gene analyses revealed that c-Myc-mediated gene expression is unique in cardiac angiogenesis and varies in a cell-dependent manner. In vitro 3-dimensional cultures demonstrated c-Myc's role in the expression of secreted angiogenic factors, while also providing evidence for c-Myc-mediated cell-cell interactions. Additional in vivo vascular analyses support c-Myc's critical role in capillary formation and vessel patterning during development and also in response to a pathological stimulus where its expression in myocytes is required for angiogenic remodeling.
  
  
  CONCLUSIONS
  These data demonstrate that proper c-Myc expression in cardiac fibroblasts and myocytes is essential to cardiac angiogenesis. These results have the potential for novel therapeutic applications involving the angiogenic response during cardiac remodeling.
authors.affiliation: Department of Medicine, Division of Molecular Cardiology, Cardiovascular Research Institute, Texas A&M Health Science Center, Temple, TX 76504, USA.
authors.forename: Colby A
authors.initials: CA
authors.lastname: Souders
authors.forename: Stephanie L K
authors.initials: SL
authors.lastname: Bowers
authors.forename: Indroneal
authors.initials: I
authors.lastname: Banerjee
authors.forename: John W
authors.initials: JW
authors.lastname: Fuseler
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Demieville
authors.forename: Troy A
authors.initials: TA
authors.lastname: Baudino
mesh_terms: D000818:Animals; D002450:Cell Communication; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D018919:Neovascularization, Physiologic / Q000235:genetics*; D016133:Polymerase Chain Reaction; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics; D012313:RNA / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D012313:RNA