Quantitation of Angiogenesis in the Chick Chorioallantoic Membrane Model Using Fractal Analysis

Kirchner, Loren M.; Schmidt, Steven; Gruber, Brian

doi:10.1006/mvre.1996.0002

Cited by 101 publications

(63 citation statements)

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“…During hemangiogenesis in the avian CAM, the vascular tree grows and fills in by a quantifiable fractal growth process (Kirchner et al, 1996;Parsons-Wingerter et al, 1998, 2000a) that can be coordinated with specific changes in generational branching of the vascular tree, as further quantified by the computer code VESGEN. Fractal-based methods developed in the CAM were successfully extended to clinical images of the adult human retina for robust, significant quantification of early-stage vascular remodeling in diabetic retinopathy (Avakian et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Lymphangiogenesis by blind‐ended vessel sprouting is concurrent with hemangiogenesis by vascular splitting

et al. 2006

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Development of effective vascular therapies requires the understanding of all modes of vessel formation involved in angiogenesis (here termed "hemangiogenesis") and lymphangiogenesis. Two major modes of vessel morphogenesis include sprouting of a new vessel from a preexisting vessel and splitting of a preexisting parent vessel into two offspring vessels. In the quail chorioallantoic membrane (CAM) during mid-development (embryonic days E6 -E9), lymphangiogenesis progressed primarily via blind-ended vessel sprouting. Isolated lymphatic endothelial progenitor cells were recruited to the tips of growing vessels. During concurrent hemangiogenesis, parent blood vessels expanded from the capillary network and split into offspring vessels, accompanied by transient capillary expression of alpha smooth muscle actin (␣SMA) and recruitment of polarized mural progenitor cells. Lymphatics and blood vessels were identified by confocal/fluorescence microscopy of vascular endothelial growth factor (VEGF) receptor VEGFR-2, ␣SMA (specific to CAM blood vessels), homeobox transcription factor Prox1 (specific to lymphatics), and the quail hematopoetic marker, QH-1. VEGFR-2 was expressed intensely in isolated cells and lymphatics, and moderately in blood vessels. Prox1 was absent from isolated progenitor cells prior to lymphatic recruitment. Exogenous vascular endothelial growth factor-165 (VEGF 165 ) increased blood vessel density and anastomotic frequency without changing endogenous modes of vascular/lymphatic vessel formation or marker expression. Although VEGF 165 is a key cellular regulator of hemangiogenesis and vasculogenesis, the role of VEGF 165 in lymphangiogenesis is less clear. Interestingly, VEGF 165 increased lymphatic vessel diameter and density as measured by novel Euclidean distance mapping, and the antimaturational dissociation of lymphatics from blood vessels, accompanied by lymphatic reassociation into homogeneous networks. Published 2006 Wiley-Liss, Inc. †

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Section: Discussionmentioning

confidence: 99%

Lymphangiogenesis by blind‐ended vessel sprouting is concurrent with hemangiogenesis by vascular splitting

et al. 2006

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“…The logic behind this index is that if all objects are oriented in the same direction, the standard deviation will be low, and if the objects are not oriented in one direction, the standard deviation will be increased. In addition, the fractal dimension of each image was calculated using the box counting method (3,30). Fractal dimension is a measure of the space-filling ability of a pattern.…”

Section: Methodsmentioning

confidence: 99%

Role of TGF-β1 and JNK signaling in capillary tube patterning

Bein¹,

Odell-Fiddler²,

Drinane³

2004

American Journal of Physiology-Cell Physiology

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factor (TGF) family of secretory polypeptides comprises signaling proteins involved in numerous physiological processes, including vascular development and vessel wall integrity. Both pro-and antiangiogenic effects of TGF-␤1 have also been documented. To study the intracellular mechanisms involved in capillary tube morphogenesis, endothelial cell aggregates were cultured in a fibrin matrix. It was found that the pattern of capillary tubes formed in a fibrin matrix was altered in response to TGF-␤1 treatment such that the capillary-like structures displayed a bipolarized pattern. In contrast, in untreated control and fibroblast growth factor-2-treated cells, the pattern of capillary tubes formed was random. TGF-␤1 also downregulated urokinase-type plasminogen activator (uPA) activity while upregulating PA inhibitor (PAI)-1 and thrombospondin (TSP)1 gene expression. To investigate the signaling cascade mediating the phenotypic changes observed, pharmacological inhibitors of p38 MAPK, Sp1 transcription factor, c-Jun NH2-terminal kinase (JNK), and the cytokine TNF-␣ were used. The p38 MAPK inhibitor SB203580 reversed the TGF-␤1-dependent inhibition of uPA activity but not its morphogenetic effect. In contrast, the DNA intercalator WP631 and TNF-␣ counteracted the TGF-␤1-induced morphogenetic effect while the JNK inhibitor SP600125 effectively inhibited capillary tube formation. These results indicate that the TGF-␤1-induced capillary tube pattern is independent of the p38 MAPK-activated PAI-1 and TSP1 expression, but the mechanism involves Sp1-dependent transcriptional regulation. The results also raise the possibility that the JNK pathway, which controls convergent extension in Xenopus, may be involved in vessel wall patterning in mammalian systems. metalloproteinase; plasminogen activator; p38 MAPK; thrombospondin 1; Sp1 THE DEVELOPMENTAL PROCESSES of blood vessel formation and organogenesis are intimately coordinated. Endothelial cells that arise from angioblast clumps, in conjunction with associated cells and the extracellular matrix, organize into a complex network of blood vessels and form a hierarchical tubular system commonly known as the vascular tree. As exemplified by the vasculature in the lungs and the heart, the vascular system develops a pattern that matches the anatomical architecture and physiological requirements of different parts of the body. The microenvironment in different vascular beds provides guidance signals that direct a given vascular pattern. Although many secreted and cell-associated molecules critical for vasculogenesis and angiogenesis are known, the cellular and molecular mechanisms underlying vascular patterning and, in particular, the cues for cellular assembly into vessels are not well understood.The matrix proteins in the microenvironment are known to modulate cellular activities. On the basis of studies performed using fibronectin, collagen, matrigel, and fibrin matrices, it has been proposed that traction forces exerted by cells on viscoelastic substrata induce reorganization ...

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“…The 'box counting' method at multiple origins 15 was applied to the image of the binary skeleton to estimate fractal dimension (D) and lacunarity (L) of the vascular network, well-known global indices of morphological complexity and structural nonuniformity, respectively. 16,17 In addition, three types of order exhibited by the CAM vessels were considered: (i) positional order, associated with the arrangement of the network in the membrane; (ii) topological order, associated with the homogeneity of branching occurrence along the structure; and (iii) orientational order, associated with the orientation of the branches forming the network. They were quantitatively evaluated starting from the image of the binary skeleton according to the following procedures.…”

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confidence: 99%

Order and disorder in the vascular network

et al. 2004

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A structural feature of particular interest in order to get a better understanding of tissue perfusion is the way a pattern of growing vessels fills the available space. To address this point, we have developed automatic image analysis methods allowing a quantitative evaluation of several parameters (fractal dimension, lacunarity and nonfractal order–disorder parameters, such as positional, topological and orientational order) characterizing the level of spatial order/disorder exhibited by the vascular network of the CAM in basal conditions and after treatment for 96 h with an angiogenic cytokine, such as fibroblast growth factor-2 (FGF-2), or with an angiostatic molecule, such as vinblastine

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Quantitation of Angiogenesis in the Chick Chorioallantoic Membrane Model Using Fractal Analysis

Cited by 101 publications

References 0 publications

Lymphangiogenesis by blind‐ended vessel sprouting is concurrent with hemangiogenesis by vascular splitting

Lymphangiogenesis by blind‐ended vessel sprouting is concurrent with hemangiogenesis by vascular splitting

Role of TGF-β1 and JNK signaling in capillary tube patterning

Order and disorder in the vascular network

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