title: Blood outgrowth endothelial cells reduce hypoxia-mediated fibroblast to myofibroblast conversion by decreasing proangiogenic cytokines.
abstract: OBJECTIVE
  Hypoxic conditions cause fibroblasts to differentiate into alpha smooth-muscle cell actin (α -SMA)-positive cells, i.e. myofibroblasts. This process is a hallmark of venous neointimal hyperplasia (VNH) associated with hemodialysis vascular access. The purpose of this study was to determine if blood outgrowth endothelial cells (BOEC) may reduce the conversion of fibroblasts into myofibroblasts under hypoxic conditions, and to determine the potential mechanisms involved.
  
  
  METHODS
  An experimental model was used, in which fibroblasts and BOEC were subjected to hypoxia under contact and transwell conditions to determine if BOEC reduce the conversion of fibroblasts into myofibroblasts under hypoxic conditions. Gene expression under different conditions was performed. In addition, functional assays including cell proliferation and migration were determined.
  
  
  RESULTS
  This study demonstrates that contact needs to occur between BOEC and fibroblasts for the reduction of the hypoxia-driven conversion of fibroblasts into α-SMA. This is associated with a decrease in several proangiogenic genes including vascular endothelial growth factor A, platelet-derived growth factor, fibroblast growth factor and matrix metalloproteinase 2 in fibroblasts in contact with BOEC when compared to fibroblasts alone. In addition, migration is significantly reduced while proliferation remains unchanged.
  
  
  CONCLUSIONS
  This study helps provide rationale for using BOEC delivered to the adventitia of the outflow vein of hemodialysis vascular access to reduce VNH.
authors: Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, Rochester, Minn., USA.
authors: Evelyn C
authors: EC
authors: Nieves Torres
authors: Binxia
authors: B
authors: Yang
authors: Akshaar
authors: A
authors: Brahmbhatt
authors: Debabrata
authors: D
authors: Mukhopadhyay
authors: Sanjay
authors: S
authors: Misra
mesh_terms: D000199:Actins / Q000378:metabolism; D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002450:Cell Communication; D015687:Cell Hypoxia; D002465:Cell Movement; D049109:Cell Proliferation; D048429:Cell Size; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D058628:Myofibroblasts / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction; D013552:Swine; D013997:Time Factors
chemical_list: D000199:Actins; D042501:Angiogenic Proteins; D016207:Cytokines; D020780:Matrix Metalloproteinase 9