On-site education of VEGF-recruited monocytes improves their performance as angiogenic and arteriogenic accessory cells

Inbal Avraham-Davidi, Simon Yona, Myriam Grunewald, Limor Landsman, Clement Cochain, Jean Sebastien Silvestre, Haim Mizrahi, Mohammad Faroja, Dalit Strauss-Ayali, Matthias Mack, Steffen Jung, Eli Keshet

Research output: Contribution to journalArticlepeer-review

Abstract

Adult neovascularization relies on the recruitment of monocytes to the target organ or tumor and functioning therein as a paracrine accessory. The exact origins of the recruited monocytes and the mechanisms underlying their plasticity remain unclear. Using a VEGFbased transgenic system in which genetically tagged monocytes are conditionally summoned to the liver as part of a VEGF-initiated angiogenic program, we show that these recruited cells are derived from the abundant pool of circulating Ly6Chi monocytes. Remarkably, however, upon arrival at the VEGF-induced organ, but not the naive organ, monocytes undergo multiple phenotypic and functional changes, endowing them with enhanced proangiogenic capabilities and, importantly, with a markedly increased capacity to remodel existing small vessels into larger conduits. Notably, monocytes do not differentiate into long-lived macrophages, but rather appear as transient accessory cells. Results from transfers of presorted subpopulations and a novel tandem transfer strategy ruled out selective recruitment of a dedicated preexisting subpopulation or onsite selection, thereby reinforcing active reprogramming as the underlying mechanism for improved performance. Collectively, this study uncovered a novel function of VEGF, namely, on-site education of recruited "standard" monocytes to become angiogenic and arteriogenic professional cells, a finding that may also lend itself for a better design of angiogenic therapies.

Original languageEnglish
Pages (from-to)2611-2625
Number of pages15
JournalJournal of Experimental Medicine
Volume210
Issue number12
DOIs
StatePublished - Nov 2013
Externally publishedYes

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