Formation of new vessels from pre-existing vessels.
Steps in Angiogenesis (4 stages):
Step 1: Stimulation of endothelial cells
by angiogenic factors.
Basic Fibroblast Growth Factor (bFGF)
1. A potent inducer of endothelial cell migration, proliferation,
and tube formation.
2. A pleiotropic factor which is not specific for endothelial
3. FGF receptor is in the tyrosine kinase family.
Endothelial Growth Factor (VEGF)
1. Highly specific for endothelial cells.
2. Inducer of extracellular proteinase expression, increased
expression of specific integrins for migration, and initiation
of cell proliferation and migration.
3. Binds to endo-specific receptors Flt-1 and Flk-1 (of the
tyrosine kinase family).
4. Expression of VEGF potentiated by hypoxia and
inactivation of p53.
Step 2: Degradation of the capillary basal
activated endothelial cells (via extracellular
1. A family of 22 zinc-dependent endopeptidases that degrade
all extracellular matrix components.
2. Subgroups of collagenases, stromelysins, gelatinases, and
3. MMP1 (a collagenase), MMP2 and MT1-MMP (basal
lamina degradation) are all expressed during angiogenesis.
1. Conversion of plasminogen (a zymogen) to plasmin (a
2. Binds cell surface receptor uPAR and get local areas of
high proteolytic activity.
3. Binding to uPAR may induce cell prolif and regulate cell
Step 3: Capillary
sprout formation and migration of
1. integrin proteins on newly forming vessels.
2. Allow migrating endothelial cells to interact with specific
components of the surrounding matrix.
1. MMps and urokinase faciliate migration of endothelium
cells into surrounding matrix.
Step 4: New
Angiopoeitin (Ang 1)
1. Produced by the surrounding stromal cells.
2. Induces endothelial cell survival and stabilization of new
3. Binds Tie2 receptor on endothelial cells and which
Platelet Derived Growth Factor (PDGF)
1. Produced by endo cells of new capi tubes.
2. Recruits pericytes (that differentiate à mature) which
interact with and stabilize the new vessels.