(A) Proteins, polysaccharides, and lipids present as free molecules in body fluids, associated to ECM, or anchored to endothelial cell membrane bind FGF2. Some of these molecules can change their status from an immobilized to a free form (gray arrows) exerting opposite effects on the biological activity of FGFs. (B) Some FGF binders are also able to interact with FGF-binding sites/receptors present on the surface of endothelial cells, possibly exerting agonist/antagonist effects.
Angiogenesis plays a key role in various physiological and pathological processes, including inflammation and tumor growth. Numerous angiogenic growth factors (AGFs) have been identified.
Usually, the angiogenic process is assumed to represent the outcome of a straightforward interaction of AGFs with specific signalling receptors of the endothelial cell (EC) surface. Actually, the mechanisms by which AGFs induce neovascularization are much more complex. Indeed, angiogenesis is the result of the simultaneous actions of various AGFs and angiogenesis modulators; multiple EC surface receptors with different structure and biological properties are engaged by AGFs to exert a full angiogenic response; AGFs bind a variety of free and immobilized proteins, polysaccharides, and complex lipids of the extracellular milieu that affect AGF integrity, stability, and bioavailability; iv) some of the AGF-binding molecules interact also with AGF receptors.
In this review we will summarize literature data and discuss the current knowledge about the extracellular molecules able to interact with AGFs, thus representing possible key regulators of the angiogenesis process. Our work represents an attempt to highlight common themes in the AGF interactome that occurs at the extracellular level during neovascularization.
Special Project Angiogenesis
EXTRACELLULAR ANGIOGENIC GROWTH FACTOR INTERACTIONS
AN ANGIOGENESIS INTERACTOME SURVEY*
*Part of this chapter is in press as:
M. Rusnati and M. Presta
"EXTRACELLULAR ANGIOGENIC GROWTH FACTOR INTERACTIONS: AN ANGIOGENESIS INTERACTOME SURVEY"
Endothelium, in press.