Blood vessel networks expand in a 2-step process that begins with vessel sprouting and is followed by vessel anastomosis. Vessel sprouting is induced by chemotactic gradients of the vascular endothelial growth factor (VEGF), which stimulates tip cell protrusion. Yet it is not known which factors promote the fusion of neighboring tip cells to add new circuits to the existing vessel network. By combining the analysis of mouse mutants defective in macrophage development or VEGF signaling with live imaging in zebrafish, we now show that macrophages promote tip cell fusion downstream of VEGF-mediated tip cell induction. Macrophages therefore play a hitherto unidentified and unexpected role as vascular fusion cells. Moreover, we show that there are striking molecular similarities between the pro-angiogenic tissue macrophages essential for vascular development and those that promote the angiogenic switch in cancer, including the expression of the cell-surface proteins TIE2 and NRP1. Our findings suggest that tissue macrophages are a target for antiangiogenic therapies, but that they could equally well be exploited to stimulate tissue vascularization in ischemic disease.

Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction / A. Fantin, J. Vieira, G. Gestri, L. Denti, Q. Schwarz, S. Prykhozhij, F. Peri, S. Wilson, C. Ruhrberg. - In: BLOOD. - ISSN 0006-4971. - 116:5(2010), pp. 829-840.

Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction

A. Fantin
Primo
;
2010

Abstract

Blood vessel networks expand in a 2-step process that begins with vessel sprouting and is followed by vessel anastomosis. Vessel sprouting is induced by chemotactic gradients of the vascular endothelial growth factor (VEGF), which stimulates tip cell protrusion. Yet it is not known which factors promote the fusion of neighboring tip cells to add new circuits to the existing vessel network. By combining the analysis of mouse mutants defective in macrophage development or VEGF signaling with live imaging in zebrafish, we now show that macrophages promote tip cell fusion downstream of VEGF-mediated tip cell induction. Macrophages therefore play a hitherto unidentified and unexpected role as vascular fusion cells. Moreover, we show that there are striking molecular similarities between the pro-angiogenic tissue macrophages essential for vascular development and those that promote the angiogenic switch in cancer, including the expression of the cell-surface proteins TIE2 and NRP1. Our findings suggest that tissue macrophages are a target for antiangiogenic therapies, but that they could equally well be exploited to stimulate tissue vascularization in ischemic disease.
Experimental choroidal neovascularization; transcription factor PU.1; blood-vessel formation; growth-factor; in-vivo; pathological angiogenesis; branching morphogenesis; mouse; gene; microglia
Settore BIO/06 - Anatomia Comparata e Citologia
Settore BIO/09 - Fisiologia
Settore BIO/13 - Biologia Applicata
Settore BIO/17 - Istologia
Article (author)
File in questo prodotto:
File Dimensione Formato  
final paper blood 5 aug 10.PDF

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 3.67 MB
Formato Adobe PDF
3.67 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/635029
Citazioni
  • ???jsp.display-item.citation.pmc??? 389
  • Scopus 698
  • ???jsp.display-item.citation.isi??? 662
social impact