title: Pericytes modulate endothelial sprouting.
abstract: OBJECTIVE
  Angiogenic sprouts arise from microvessels formed by endothelial cells (ECs) invested by pericytes (PCs). The aim of this study was to examine the role of PCs in angiogenic sprouting, an understudied phenomenon.
  
  
  RESULTS
  We adapted a human EC spheroid model to examine PC effects on vascular endothelial growth factor-A-induced EC sprouting in vitro by using Bcl-2-transduced human umbilical vein ECs to reduce apoptosis in collagen gels. Human placental PCs, separated from endothelial spheroids by a transwell, or addition of PC-conditioned media increased EC sprouting primarily through hepatocyte growth factor (HGF). Mixed endothelial-PC spheroids formed similar numbers of endothelial sprouts as endothelial spheroids but the sprouts from mixed spheroids were invested by PCs within 24 h. PCs were recruited to the sprouts by platelet-derived growth factor (PDGF)-BB; inhibition of PDGF signalling reduced PC coverage and increased EC sprouting. Transplanted endothelial spheroids give rise to sprouts in vivo that evolve into perfused microvessels. Mixed endothelial-PC spheroids form similar numbers of microvessels as endothelial-only spheroids, but acquire human PC investment and have reduced average lumen diameter.
  
  
  CONCLUSIONS
  PCs promote endothelial sprouting by elaborating HGF, but when recruited to invest endothelial sprouts by PDGF-BB, limit the extent of sprouting in vitro and lumen diameter in vivo.
authors.affiliation: Department of Medicine and Section of Nephrology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Chang
authors.forename: Jillian W
authors.initials: JW
authors.lastname: Andrejecsk
authors.forename: Martin S
authors.initials: MS
authors.lastname: Kluger
authors.forename: W Mark
authors.initials: WM
authors.lastname: Saltzman
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Pober
mesh_terms: D000077214:Becaplermin; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D055806:Microvessels / Q000166:cytology / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D019899:Paracrine Communication; D020286:Pericytes / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D015398:Signal Transduction; D018874:Spheroids, Cellular; D013997:Time Factors; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; C066855:HGF protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D020574:Proto-Oncogene Proteins c-sis; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077214:Becaplermin; D017228:Hepatocyte Growth Factor
keywords: Bcl-2; Endothelial cells; Hepatocyte growth factor; Pericytes; Platelet-derived growth factor
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