Angiogenesis stimulating protein

Blockade of angiogenesis is useful in tumor therapy (Ferrara and Kerbel 2005 Menakuru et al. 2008). Over the last decade, the most extensively examined proan-giogenic molecule has been VEGF, a secreted protein that, through activation of tyrosine kinase receptors, promotes key events in angiogenesis that include increases in vascular permeability, and stimulation of endothelial cell proliferation and migration (Ferrara 2003). 

A recently identified thyroid hormone cell surface receptor on the extracellular domain of integrin alphaVbeta (3) leads to the activation of the mitogen-activated protein kinase (MAPK) signal transduction cascade in human cell lines, Examples of MAPK-dependent thyroid hormone actions are plasma membrane ion pump stimulation and specific nuclear events, These events include serine phosphorylation of the nuclear thyroid hormone receptor, leading to co-activator protein recruitment and complex tissue responses, such as thyroid hormone-induced angiogenesis, The existence of this cell surface receptor means that the activity of the administered hormone could be limited through structural modification of the molecule to reproduce only those hormone actions initiated at the cell surface (8,9). 

Desai A, Victor-Vega C, Gadangi S, et al. Adenosine A2A receptor stimulation increases angiogenesis by down-regulating production of the antiangiogenic matrix protein thrombospondin I. Mol Pharmacol 2005 67 1406-1413. 

The FGF family consists of 23 proteins that are classified by their expression pattern, receptor-binding preference, and protein sequence (20,21). FGF is present in the normal myocardium (22). Its expression is stimulated by hypoxia (23) and hemodynamic stress (24). FGF-2 is a pluripotent molecule and modulates numerous cellular functions for multiple cell types. In the context of angiogenesis, it induces endothelial cell proliferation, survival, and differentiation, and is also involved in cell migration of endothelial cells, smooth muscle cells, macrophages, and fibroblasts (21). These effects are mediated through its interaction with the tyrosine kinase receptor FGFRI which also leads to the downstream release of NO (25). Additionally, FGF-2 stimulates endothelial cells to produce a... 

The recent identification of lysoPLD as autotaxin (ATX) has been particularly helpful for understanding LPA pathways. ATX was first identified as a protein in melanoma cell culture medium that stimulated cancer cell motility (Murata et al. 1994 Stracke et al. 1992). ATX has a single transmembrane domain, two somatomedin B-like domains, and a catalytic domain (Stracke et al. 1997). ATX is most likely cleaved intracellularly, then released into the extracellular environment. ATX was initially proposed to function as a nucleotide phosphodiesterase, but the role of this activity in ATX function is currently unclear (Bollen et al. 2000 Coding et al. 1998). In addition to its ability to promote cancer cell motility, ATX has also been shown to promote angiogenesis in vivo (Nam et al. 2001). These results support the view that ATX is an important factor in cancer biology. 

Fibroblast growth factor protein has been infused into the coronary arteries, or injected directly into the heart muscle. Because of poor FGF protein pharmacokinetics (i.e., low retention by the heart) [18], stimulation of myocardial angiogenesis requires high doses of FGF protein intracoronary infusion over a long period of time. 

In addition to the growth factors that stimulate this process, there are several other proteins that inhibit the formation of new blood vessels. In fact, the normal process of angiogenesis is dependent on the appropriate balance of the stimulatory growth factors and the Inhibitory proteins. 

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