Endothelial struts enable the generation of large lumenized blood vessels de novo

Bart Weijts, Iftach Shaked, Mark Ginsberg, David Kleinfeld, Catherine Robin, David Traver

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

De novo blood vessel formation occurs through coalescence of endothelial cells (ECs) into a cord-like structure, followed by lumenization either through cell-1-3 or cord-hollowing4-7. Vessels generated in this manner are restricted in diameter to one or two ECs, and these models fail to explain how vasculogenesis can form large-diameter vessels. Here, we describe a model for large vessel formation that does not require a cord-like structure or a hollowing step. In this model, ECs coalesce into a network of struts in the future lumen of the vessel, a process dependent upon bone morphogenetic protein signalling. The vessel wall forms around this network and consists initially of only a few patches of ECs. To withstand external forces and to maintain the shape of the vessel, strut formation traps erythrocytes into compartments to form a rigid structure. Struts gradually prune and ECs from struts migrate into and become part of the vessel wall. Experimental severing of struts resulted in vessel collapse, disturbed blood flow and remodelling defects, demonstrating that struts enable the patency of large vessels during their formation.

Original languageEnglish
Pages (from-to)322-329
Number of pages8
JournalNature Cell Biology
Volume23
Issue number4
DOIs
Publication statusPublished - Apr 2021

Keywords

  • Blood Vessels/growth & development
  • Endothelial Cells/metabolism
  • Erythrocytes/metabolism
  • Humans
  • Morphogenesis/genetics
  • Neovascularization, Physiologic/genetics

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