Angiogenesis Stimulation

Once the proteolysis or basement membrane breakdown takes place the endothelial cells start to migrate through the broken areas. These cells are stimulated by a variety of growth factors.

These are released by the extracellular matrix (ECM). The angiogenesis factors are divided into three classes.

The first class consists of the VEGF family and the angiopoietins. These act especially on the endothelial cells.

VEGF belongs to the VEGF family. There are six members in this family. These include VEGF-A (or VEGF), PlGF, VEGF-B, VEGF-C, VEGF-D, and orf virus VEGF (VEGF-E).

VEGF is vital for survival and development of the fetus. VEGF works by stimulating the breakdown of the ECM along with multiplication, movement and tube formation of endothelial cells. It helps these cells express uPA, PAI-1, uPAR, and MMP-1.

The second class contains direct-acting molecules like cytokines, chemokines and angiogenic enzymes. These target other cells as well.

One of the members of this group is the FGF-2 that was one of the first angiogenic peptides to be characterized. The FGF family has 19 members.

FGF 2 is vital for angiogenesis. It induces multiplication and movement of the cells as well as uPA production by endothelial cells. FGF-2 induces tube formation in collagen gels and alters integrin expression that helps in angiogenesis.

The third group of angiogenic molecules are indirect-acting factors that act by release of direct-acting factors from macrophages, endothelial or tumor cells rather than directly on the endothelial cells. Agents of this group include tumor necrosis factors (TNF a and b).