The Angiogenesis Process: How Do New Blood Vessels Grow?
The
process of angiogenesis occurs as an orderly series of events:
- Diseased or injured tissues
produce and release angiogenic growth factors (proteins) that diffuse
into the nearby tissues.
- The angiogenic growth factors
bind to specific receptors located on the endothelial cells (EC) of
nearby preexisting blood vessels.
- 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. These enzymes dissolve tiny holes
in the sheath-like covering (basement membrane) surrounding all existing
blood vessels.
- The endothelial cells begin
to divide (proliferate) and migrate out through the dissolved
holes of the existing vessel towards the diseased tissue (tumor).
- Specialized molecules called
adhesion molecules called integrins (avb3, avb5) serve as grappling hooks
to help pull the sprouting new blood vessel sprout forward.
- Additional enzymes (matrix
metalloproteinases, or MMP) 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.
- Sprouting endothelial cells
roll up to form a blood vessel tube.
- Individual blood vessel
tubes connect to form blood vessel loops that can circulate blood.
- Finally, newly formed blood
vessel tubes are stabilized by specialized muscle cells (smooth muscle
cells, pericytes) that provide structural support. Blood flow then begins.
Last updated September 7, 2011
References:
Folkman J, D’Amore PA. Blood vessel formation: what is its molecular basis? Cell 1996;87:1153-1155.
Folkman J, Hanahan D. Expression of the angiogenic pheno-type during development of murine and human cancer, in Origins of Human Cancer: A Comprehensive Review. Brugge J, Curran T, Harlow E, et al, eds. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1991:pp.803-814.
Risau W. Mechanisms of angiogenesis. Nature 1997;386:671-674. |
