Angiogenic Process

Increases in vascular density, tissue blood volume, or blood flow may be useful outcome measures of angiogenesis. However, vascular density is also modulated by vascular regression and changes in the perivascular tissue such as edema matrix synthesis and cellular proliferation, infiltration, and apoptosis. Blood flow is particularly confounded by vascular tone, and many angiogenic factors are also vasodilators. It may be difficult to distinguish angiogenesis from the increased blood flow that is associated with inflammation. 

In summary, the complexity of the angiogenic process has led to a wide range of indexes of angiogenesis which may be best considered together rather than each in isolation in order to gain a deep understanding of vascular growth. 

Regulation of the later stages of angiogenesis may be particularly important in highly differentiated tissues and the close relationship between hypoxia and angiogenesis provides a neat mechanism by which perfusion can be matched to the oxygen requirements of the tissue [11]. However, proliferation of blood vessels may itself impair the function of some tissues. For example, vascularization leads to opacification in the cornea. Vascularization of the articular cartilage impairs its biomechanical characteristics and leads to endochondral bone formation [6], 

Any increase in angiogenesis in articular tissues may disturb an already precarious balance between perfusion, metabolic demand, and structural 

VEGF as a Prototypical Direct-Acting Angiogenic Factor 

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The angiogenic process involves not only endothelial cells but also many other cell types and signals coming from other districts of the organism. Therefore in vivo studies are a necessary checkpoint of any experimentation of angiogenic stimulators or inhibitors. 

Passaniti et al described a simple adaptation of the cutaneous implant assays using reconstituted BMs (Passaniti et al., 1992). The group of Albini in Genova (1) has extensively used reconstituted BMs to study specific steps of the angiogenic process in vitro and assess angiogenesis in vivo (Albini et al., 1994, 1995 Benelli et al., 1994 lurlaro et al., 1998). The use of reconstituted BMs has several advantages both in vitro and in vivo. 

It has been shown that combretastatin A-4 disrupts the microtubules of human umbilical vein endothelial cells (HUVECs) in culture, thus confirming that the tubulin binding properties shown in cell-free systems are retained when the compound enters cells and that tubulin binding is a significant component of the biological activity. Also 3-fluoro- and 3-chloro derivatives retained activity in human umbilical vein endothelial cells. This kind of activity against endothelial cells is extremely important, as endothelial cells play a key role in the angiogenic process. 

There is abundant evidence that the receptor CXCR2 regulates the angiogenic process in a number of model systems. Gene knockout or antibody blockade of CXCR2 prevented CXC chemokine-mediated angiogenesis in a corneal micropocket assay [2]. Subsequently, it was shown that blockade of CXCR2 function disrupted endothelial cell chemotaxis and tube formation... 

Folkman, J. (2003) Fundamental concepts of the angiogenic process. Current Molecular Medicine, 3, 643-651. 

The significance of the angiogenic process increases considerably every year as new findings reveal novel mechanisms through which this process can modulate disease development and recovery [10]. 

Angiogenesis is the formation of new blood vessel from existing vasculature, an adaptive process to compensate tissue and cellular requirement for oxygen and nutrient import as much as the need to export metabolic wastes, and thus considered critical for growth and survival of tumors. Angiogenesis is also a prerequisite for metastatic tumor spread. As a result, intervention of the angiogenic process by... 

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