title: Pericyte regulation of vascular remodeling through the CXC receptor 3.
abstract: OBJECTIVE
  To understand the role, if any, played by pericytes in the regulation of newly formed vessels during angiogenesis. In this study, we investigate whether pericytes regulate the number of nascent endothelial tubes.
  
  
  RESULTS
  Using an in vitro angiogenesis assay (Matrigel assay), we demonstrate that pericytes can inhibit vessel formation and induce vessel dissociation via CXCR3-induced involution of the endothelial cells. In a coculture Matrigel assay for cord formation, pericytes prevented endothelial cord formation of human dermal microvascular endothelial cells but not umbilical vein endothelial cells. Blockade of endothelial CXCR3 function or expression inhibited the repressing effect of the pericytes. We further show that pericytes are also able to induce regression of newly formed microvascular cords through CXCR3 activation of calpain. When CXCR3 function was inhibited by a neutralizing antibody or downregulated by siRNA, cord regression mediated by pericytes was abolished.
  
  
  CONCLUSIONS
  We show for the first time that pericytes regulate angiogenic vessel formation, and that this is mediated through CXCR3 expressed on endothelial cells. This suggests a role for pericytes in the pruning of immature vessels overproduced during wound repair.
authors.affiliation: From the Department of Pathology (R.J.B., M.E.B., A.W.) and Department of Bioengineering (W.C.W.C.), University of Pittsburgh, PA; and Pittsburgh Veterans Affairs Medical Center, Pittsburgh, PA (R.J.B., M.E.B., A.W.).
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Bodnar
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Rodgers
authors.forename: William C W
authors.initials: WC
authors.lastname: Chen
authors.forename: Alan
authors.initials: A
authors.lastname: Wells
mesh_terms: D002154:Calpain / Q000378:metabolism; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism*; D004789:Enzyme Activation; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008024:Ligands; D018919:Neovascularization, Physiologic; D020286:Pericytes / Q000276:immunology / Q000378:metabolism*; D034622:RNA Interference; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D014945:Wound Healing
chemical_list: C515187:CXCR3 protein, human; D008024:Ligands; D054367:Receptors, CXCR3; D007371:Interferon-gamma; D002154:Calpain
keywords: CXC chemokine receptor 3; angiogenesis; endothelial cells; pericytes; wound healing