VEGF-induced adult neovascularization: Recruitment, retention, and role of accessory cells

Myriam Grunewald, Inbal Avraham, Yuval Dor, Esther Bachar-Lustig, Ahuva Itin, Steffen Yung, Stephano Chimenti, Limor Landsman, Rinat Abramovitch, Eli Keshet*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1037 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)175-189
Number of pages15
JournalCell
Volume124
Issue number1
DOIs
StatePublished - 13 Jan 2006
Externally publishedYes

Funding

FundersFunder number
Ministry of Science, Israel
Israel Cancer Research Fund
Israel Science Foundation

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