Blood vessel endothelial VEGFR-2 delays lymphangiogenesis: an endogenous trapping mechanism links lymph- and angiogenesis.

Article Details

Citation

Nakao S, Zandi S, Hata Y, Kawahara S, Arita R, Schering A, Sun D, Melhorn MI, Ito Y, Lara-Castillo N, Ishibashi T, Hafezi-Moghadam A

Blood vessel endothelial VEGFR-2 delays lymphangiogenesis: an endogenous trapping mechanism links lymph- and angiogenesis.

Blood. 2011 Jan 20;117(3):1081-90. doi: 10.1182/blood-2010-02-267427. Epub 2010 Aug 12.

PubMed ID
20705758 [ View in PubMed
]
Abstract

Angio- and lymphangiogenesis are inherently related processes. However, how blood and lymphatic vessels regulate each other is unknown. This work introduces a novel mechanism explaining the temporal and spatial relation of blood and lymphatic vessels. Vascular endothelial growth factor-A (VEGF-A) surprisingly reduced VEGF-C in the supernatant of blood vessel endothelial cells, suggesting growth factor (GF) clearance by the growing endothelium. The orientation of lymphatic sprouting toward angiogenic vessels and away from exogenous GFs was VEGF-C dependent. In vivo molecular imaging revealed higher VEGF receptor (R)-2 in angiogenic tips compared with normal vessels. Consistently, lymphatic growth was impeded in the angiogenic front. VEGF-C/R-2 complex in the cytoplasm of VEGF-A-treated endothelium indicated that receptor-mediated internalization causes GF clearance from the extracellular matrix. GF clearance by receptor-mediated internalization is a new paradigm explaining various characteristics of lymphatics.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Vascular endothelial growth factor receptor 2P35968Details