1 research outputs found
Supplementary Material for: Blood Outgrowth Endothelial Cells Reduce Hypoxia-Mediated Fibroblast to Myofibroblast Conversion by Decreasing Proangiogenic Cytokines
<p><b><i>Purpose:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b>
This study helps provide rationale for using BOEC delivered to the
adventitia of the outflow vein of hemodialysis vascular access to reduce
VNH.</p