Blood vessel endothelial vegfr-2 delays lymphangiogenesis: An endogenous trapping mechanism links lymph- and angiogenesis

Shintaro Nakao, Souska Zandi, Yasuaki Hata, Shuhei Kawahara, Ryoichi Arita, Alexander Schering, Dawei Sun, Mark I. Melhorn, Yasuhiro Ito, Nuria Lara-Castillo, Tatsuro Ishibashi, Ali Hafezi-Moghadam

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34 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1081-1090
Number of pages10
Issue number3
Publication statusPublished - Jan 20 2011


All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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