Extracellular matrix mediates a molecular balance between vascular morphogenesis and regression.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Davis
George E
GE
Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, Missouri 65212, USA. DavisGeo@missouri.edu
Senger
Donald R
DR
D002450:Cell Communication / Q000502:physiology*; D003094:Collagen / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D003094:Collagen; D020782:Matrix Metalloproteinases