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Angiogenesis


Scope of this initiative within the CMB:

Angiogenesis, the process of new blood vessel formation from pre-existing vessels, plays a relevant role during both physiological (i.e. wound healing, tissue remodeling, embryo development) as well as pathological (i.e. tumor growth and development) events. To occur, angiogenesis requires distinct events that include endothelial cell proliferation, migration and assembly into functional vessels. Each of these steps can be regulated by different factors, such as growth factors, cytokines, and extracellular matrix-derived products. Among the growth factors, VEGF, angiopoietins and b-FGF are the best known and best characterized pro-angiogenic molecules. These growth factors bind to receptors (tyrosine kinase receptors) thus activating different signal transductions pathways, including activation of ERK (necessary to support proliferation), p38 (necessary to support migration) and PI3K/Akt (necessary to support survival). Overall these growth factors are known as positive regulators of angiogenesis and play a role in “switching” endothelial cells from quiescent to angiogenic.

As it can be stimulated, angiogenesis can also be inhibited by the so called negative regulators of angiogenesis. Among these inhibitors, angiostatin (a cleavage products of plasminogen), endostatin (a cleavage of collagen XVIII) and cleavage products of collagen IV seem to have a potent anti-angiogenic activity both in vivo and in vitro. These cleavage products seem to prevent endothelial cell functions by interacting with integrins, transmembrane receptors for extracellular matrix components. Angiostatin, endostatin, and some cleavage products of collagen IV, for example, have been found to interact with integrin αVβ3, a receptor expressed primarily by angiogenic blood vessels, reducing cell migration and tube formation.

As collagen XVIII and collagen IV are the major components of vascular basement membranes, the identification of extracellular matrix-derived cleavage products able to inhibit angiogenesis, make them attractive candidate targets for situations in which angiogenesis is unwanted, such as tumor angiogenesis.

The CMB will promote exchange of information and matrix reagents among Vanderbilt investigators interested directly or peripherally in angiogenesis studies.

 

  Members (16)

Borza, Dorin-Bogdan
Chen, Jin
Davidson, Jeffrey M.
Hudson, Billy G.
Lin, Charles
Manousaki, Daphne
Penn, John S.
Pozzi, Ambra
Quaranta, Vito
Richmond, Ann
Zent, Roy
Zutter, Mary M.


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