VEGF-induced adult neovascularization: recruitment, retention, and role of accessory cells.
Adult neovascularization relies on the recruitment of circulating cells, but their angiogenic roles and recruitment mechanisms are unclear. We show that the endothelial growth factor VEGF is sufficient for organ homing of circulating mononuclear myeloid cells and is required for their perivascular positioning and retention. Recruited bone marrow-derived circulating cells (RBCCs) summoned by VEGF serve a function distinct from endothelial progenitor cells. Retention of RBCCs in close proximity to angiogenic vessels is mediated by SDF1, a chemokine induced by VEGF in activated perivascular myofibroblasts. RBCCs enhance in situ proliferation of endothelial cells via secreting proangiogenic activities distinct from locally induced activities. Precluding RBCCs strongly attenuated the proangiogenic response to VEGF and addition of purified RBCCs enhanced angiogenesis in excision wounds. Together, the data suggest a model for VEGF-programmed adult neovascularization highlighting the essential paracrine role of recruited myeloid cells and a role for SDF1 in their perivascular retention.
Grunewald
Myriam
M
Department of Molecular Biology, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
Avraham
Inbal
I
Dor
Yuval
Y
Bachar-Lustig
Esther
E
Itin
Ahuva
A
Jung
Steffen
S
Yung
Steffen
S
Chimenti
Stephano
S
Landsman
Limor
L
Abramovitch
Rinat
R
Keshet
Eli
E
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000502:physiology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000187:drug effects / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D009928:Organ Specificity / Q000235:genetics / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology / Q000502:physiology*
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D042461:Vascular Endothelial Growth Factor A