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Circulation Research. 2005;97:1093-1107
doi: 10.1161/01.RES.0000191547.64391.e3
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(Circulation Research. 2005;97:1093.)
© 2005 American Heart Association, Inc.


Review

Endothelial Extracellular Matrix

Biosynthesis, Remodeling, and Functions During Vascular Morphogenesis and Neovessel Stabilization

George E. Davis, Donald R. Senger

From the Department of Pathology (G.E.D.), Texas A&M University System Health Science Center, College Station; and Department of Pathology (D.R.S.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass.

Correspondence to Donald R. Senger, Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Research North, 99 Brookline Ave, Boston, MA 02215. E-mail dsenger{at}bidmc.harvard.edu

Guest Editor: This Review is part of a thematic series on Vascular Cell Diversity, which includes the following articles:

Heart Valve Development: Endothelial Cell Signaling and Differentiation
Molecular Determinants of Vascular Smooth Muscle Cell Diversity
Endothelial/Pericyte Interactions


Endothelial Extracellular Matrix: Biosynthesis, Remodeling, and Functions During Vascular Morphogenesis and Neovessel Stabilization
Joyce Bischoff

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.


Key Words: extracellular matrix • endothelial cells • angiogenesis • vascular morphogenesis • vessel stabilization




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