How Do New Blood Vessels Grow?
The process of angiogenesis occurs as an orderly series of events:
1. Diseased or injured tissues
produce and release angiogenic growth factors (proteins) that diffuse
into the nearby tissues.
2. The angiogenic growth factors bind to specific
receptors located on the endothelial cells of nearby pre-existing blood
3. Once growth factors bind to their receptors,
the endothelial cells become activated. Signals are sent from the cell's
surface to the nucleus. The endothelial cell's machinery begins to produce
new molecules including enzymes.
4. Enzymes dissolve tiny holes in the sheath-like
covering (basement membrane) surrounding all existing blood vessels.
5. The endothelial cells begin to divide (proliferate),
and they migrate out through the dissolved holes of the existing vessel
towards the diseased tissue (tumor).
6. Specialized molecules called adhesion molecules,
(vß3, vß5) serve as grappling hooks to help pull the sprouting
new blood vessel sprout forward.
7. Additional enzymes (matrix metalloproteinases)
are produced to dissolve the tissue in front of the sprouting vessel tip
in order to accommodate it. As the vessel extends, the tissue is remolded
around the vessel.
8. Sprouting endothelial cells roll up to
form a blood vessel tube.
9. Individual blood vessel tubes connect to
form blood vessel loops that can circulate blood.
10. Finally, newly-formed blood vessel tubes
are stabilized by specialized muscle cells (smooth muscle cells, pericytes)
that provide structural support. Blood flow then begins.