Extracellular matrix mediates a molecular balance between vascular morphogenesis and regression

Curr Opin Hematol. 2008 May;15(3):197-203. doi: 10.1097/MOH.0b013e3282fcc321.


Purpose of review: We discuss very recent studies that address the critical role of extracellular matrix in controlling the balance between vascular morphogenesis and regression. Much of this work suggests that a balance mechanism exists for controlling the extent of tissue vascularization involving downstream signaling events regulating endothelial cell behaviors in relation to their interactions with extracellular matrix molecules.

Recent findings: Endothelial gene expression changes and signaling lead to events that not only stimulate vascular morphogenesis but also suppress mechanisms mediated through pro-regression factors such as Rho kinase. At the same time, vascular networks are susceptible to regression mediated by factors such as matrix metalloproteinase-1, matrix metalloproteinase-10, thrombospondin-1, extracellular matrix matricryptic fragments and angiopoietin-2. Pericyte recruitment to such vascular tubes can prevent regression events by delivering molecules such as tissue inhibitor of metalloproteinase-3 and angiopoietin-1 that promote vascular stabilization by decreasing tube susceptibility to these regression stimuli.

Summary: Extracellular matrix-derived signals lead to critical morphologic changes mediated through cytoskeletal rearrangements that control the shape, function and signaling events in endothelial cell-lined vessels regulating tube formation, remodeling, stabilization and regression. These signals control both vascular morphogenic and regression events, and thus a molecular balance exists to control the extent and function of vascular tube networks within tissues.

Publication types

  • Review

MeSH terms

  • Cell Communication / physiology*
  • Collagen / physiology
  • Extracellular Matrix / physiology*
  • Humans
  • Matrix Metalloproteinases / physiology
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Physiologic / physiology*
  • Signal Transduction / physiology


  • Collagen
  • Matrix Metalloproteinases