On-site education of VEGF-recruited monocytes improves their performance as angiogenic and arteriogenic accessory cells.
J Exp Med
; 210(12): 2611-25, 2013 Nov 18.
Article
em En
| MEDLINE
| ID: mdl-24166715
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 VEGF-based 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 Ly6C(hi) 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Monócitos
/
Neovascularização Fisiológica
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Fator A de Crescimento do Endotélio Vascular
Limite:
Animals
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Israel