Cellular changes in normal blood capillaries undergoing regression after inhibition of VEGF signaling

Am J Physiol Heart Circ Physiol. 2006 Feb;290(2):H547-59. doi: 10.1152/ajpheart.00616.2005. Epub 2005 Sep 19.


The vasculature of the embryo requires vascular endothelial growth factor (VEGF) during development, but most adult blood vessels lose VEGF dependence. However, some capillaries in the respiratory tract and selected other organs of adult mice regress after VEGF inhibition. The present study sought to identify the sequence of events and the fate of endothelial cells, pericytes, and vascular basement membrane during capillary regression in mouse tracheas after VEGF signaling was blocked with a VEGF-receptor tyrosine kinase inhibitor AG-013736 or soluble receptor construct (VEGF Trap or soluble adenoviral VEGFR-1). Within 1 day, patency was lost and fibrin accumulated in some tracheal capillaries. Apoptotic endothelial cells marked by activated caspase-3 were present in capillaries without blood flow. VEGF inhibition was accompanied by a 19% decrease in tracheal capillaries over 7 days and 30% over 21 days. During this period, desmin/NG2-immunoreactive pericytes moved away from regressing capillaries onto surviving vessels. Empty sleeves of basement membrane, left behind by regressing endothelial cells, persisted for about 2 wk and served as a scaffold for vascular regrowth after treatment ended. The amount of regrowth was limited by the number of surviving basement membrane sleeves. These findings demonstrate that, after inhibition of VEGF signaling, some normal capillaries regress in a systematic sequence of events initiated by a cessation of blood flow and followed by apoptosis of endothelial cells, migration of pericytes away from regressing vessels, and formation of empty basement membrane sleeves that can facilitate capillary regrowth.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Axitinib
  • Basement Membrane / metabolism
  • Capillaries / cytology*
  • Capillaries / growth & development
  • Capillaries / metabolism
  • Capillaries / physiology*
  • Collagen Type IV / metabolism
  • Endothelial Cells / cytology
  • Endothelial Cells / physiology
  • Imidazoles
  • Indazoles / pharmacology*
  • Mice
  • Mice, Inbred Strains
  • Pericytes / cytology
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Signal Transduction / drug effects*
  • Trachea / blood supply
  • Vascular Endothelial Growth Factor A / metabolism*
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism*
  • Vascular Patency / drug effects


  • Collagen Type IV
  • Imidazoles
  • Indazoles
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Vascular Endothelial Growth Factor A
  • Axitinib
  • Vascular Endothelial Growth Factor Receptor-1