Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization.
The extracellular matrix (ECM) is critical for all aspects of vascular biology. In concert with supporting cells, endothelial cells (ECs) assemble a laminin-rich basement membrane matrix that provides structural and organizational stability. During the onset of angiogenesis, this basement membrane matrix is degraded by proteinases, among which membrane-type matrix metalloproteinases (MT-MMPs) are particularly significant. As angiogenesis proceeds, ECM serves essential functions in supporting key signaling events involved in regulating EC migration, invasion, proliferation, and survival. Moreover, the provisional ECM serves as a pliable scaffold wherein mechanical guidance forces are established among distal ECs, thereby providing organizational cues in the absence of cell-cell contact. Finally, through specific integrin-dependent signal transduction pathways, ECM controls the EC cytoskeleton to orchestrate the complex process of vascular morphogenesis by which proliferating ECs organize into multicellular tubes with functional lumens. Thus, the composition of ECM and therefore the regulation of ECM degradation and remodeling serves pivotally in the control of lumen and tube formation and, finally, neovessel stability and maturation.
Davis
George E
GE
Department of Pathology, Texas A&M University System Health Science Center, College Station, USA.
Senger
Donald R
DR
D000818:Animals; D001808:Blood Vessels / Q000196:embryology*; D002196:Capillaries; D002450:Cell Communication; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000502:physiology; D007797:Laminin / Q000502:physiology; D020781:Matrix Metalloproteinase 1 / Q000502:physiology; D053506:Matrix Metalloproteinase 10; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000502:physiology; D009024:Morphogenesis / Q000502:physiology*; D018919:Neovascularization, Physiologic; D015398:Signal Transduction / Q000502:physiology*
D016207:Cytokines; D016023:Integrins; D007797:Laminin; D017868:Cyclic AMP-Dependent Protein Kinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D053506:Matrix Metalloproteinase 10; D020781:Matrix Metalloproteinase 1