Angiogenesis

Abstract

Extracellular matrix (ECM) is essential for all stages of angiogenesis. In the adult, angiogenesis begins with endothelial cell (EC) activation, degradation of vascular basement membrane, and vascular sprouting within interstitial matrix. During this sprouting phase, ECM binding to integrins provides critical signaling support for EC proliferation, survival, and migration. ECM also signals the EC cytoskeleton to initiate blood vessel morphogenesis. Dynamic remodeling of ECM, particularly by membrane-type matrix metalloproteases (MT-MMPs), coordinates formation of vascular tubes with lumens and provides guidance tunnels for pericytes that assist ECs in the assembly of vascular basement membrane. ECM also provides a binding scaffold for a variety of cytokines that exert essential signaling functions during angiogenesis. In the embryo, ECM is equally critical for angiogenesis and vessel stabilization, although there are likely important distinctions from the adult because of differences in composition and abundance of specific ECM components.T he extracellular matrix (ECM) provides a critical framework for angiogenesis through structural support and also by conferring molecular signals essential for all stages of blood vessel formation, including vascular sprouting, lumen formation, vessel maturation, and ultimately vessel stabilization. In addition, ECM provides an immobilizing scaffold for cytokines that are important for angiogenesis. Thus, by providing basic structural support, direct signaling functions, and scaffolding for cytokines, ECM exerts fundamental control over angiogenesis. Moreover, the established functional complexity of ECM together with known mechanisms available for dynamic ECM remodeling suggest that ECM is capable of exerting precise control over all aspects of angiogenesis and blood vessel maturation.This article is divided into four parts: (1) Overview of angiogenesis and ECM in the adult; (2) key functions of ECM during angiogenesis; (3) distinctions between the composition of embryonic and adult ECMs, including implications for the involvement of specific integrins in angiogenesis; and (4) ECM remodeling during vascular tube formation and stabilization. The scientific literature on ECM and angiogenesis is vast, and it is therefore impossible to cover this topic completely in a single article. Thus, rather than striving for an exhaustive review of

Oxidized Low‐Density Lipoprotein Alters the Effect of Matrix Stiffness on the Formation of Endothelial Networks and Capillary Lumens

“…As described above, the lumens that were observed in our study were relatively homogenous in size, being formed from either single cells or pairs of cells with the size distribution between 50 and 200 μm 2 , as was described in earlier studies. 3,25,28 It was also shown earlier that these lumens are formed from intracellular vacuoles that subsequently coalesce to form intracellular lumens, which then merge further to form multicellular capillary tubes. 3,25,28 In contrast, blood vessels that were observed by Critser et al 27 in collagen plugs in vivo were highly variable, ranging from small vessels to large multicellular structures of up to 4,000 μm 2 .…”

“…3,25,28 It was also shown earlier that these lumens are formed from intracellular vacuoles that subsequently coalesce to form intracellular lumens, which then merge further to form multicellular capillary tubes. 3,25,28 In contrast, blood vessels that were observed by Critser et al 27 in collagen plugs in vivo were highly variable, ranging from small vessels to large multicellular structures of up to 4,000 μm 2 . We suggest, therefore, that an increase in collagen has a differential effect on the formation of single-cell capillaries observed in our study versus multicellular structures observed previously in vivo.…”

“…The stiffness of the extracellular matrix has a major effect on angiogenesis, a process of formation of new capillaries, [1][2][3] suggesting that tissue fibrosis plays an important role in the abnormalities of capillary formation. A clinical example is progressive systemic sclerosis (PSS), or scleroderma, a disease that is characterized by loss and distortion of capillaries and other small blood vessels, 4,5 as well as extensive collagen deposition and profound stiffness of several organ systems.…”

Apolipoprotein E Inhibits Cerebrovascular Pericyte Mobility through a RhoA Protein-mediated Pathway

“…In addition to glial scar formation, the migration of pericytes is critically involved in the angiogenesis process (35), where pericytes are recruited to endothelial cell-lined tubes along the ablumenal surface to facilitate vessel maturation by inducing vascular basement membrane matrix deposition (36). Because angiogenesis is essential during development and organ repair, the imbalance in the angiogenesis process contributes to numerous human disorders, including cancer, diabetes, infection, and ischemic diseases (37).…”

Integrins in Wound Healing

“…Injury to the tissue also initiates angiogenesis (formation of new blood vessels from pre-existing blood vessels). 12 Wound angiogenesis is tightly associated with granulation tissue formation and has many similarities to re-epithelialization. Similarly to the epithelial cells, the endothelial cells or their precursor cells in the pre-existing blood vessels become activated by cytokines and start to migrate to the wound provisional matrix.…”