Angiogenesis is the formation of new blood vessels from pre-existing blood vessels. Angiogenesis may take place in two ways - endothelial sprouting or non-sprouting (intussusceptive).
Endothelial sprouting or sprouting angiogenesis
Sprouting angiogenesis is the basic mechanism seen in the growth of new blood vessels. It was the first identified form of angiogenesis. It occurs in several well-characterized stages.
There are sequential steps that are finely regulated by chemical mediators in the body. Significant role is played by factors such as Notch, Wnt, VEGF (Vascular Endothelial Growth Factors).
Some of the steps in sprouting endothelial factors include:-
- The first step is appearance of the angiogenic growth factors. These in turn activate receptors present on endothelial cells. The endothelial cells line the blood vessels of existing cells.
- Next these activated endothelial cells begin to release enzymes like proteases. These proteases can break down proteins and cells of the basement membrane. This creates opening in the existing blood vessel that allows the outpouring of the activated endothelial cells from the existing parent blood vessel.
- Once these endothelial cells have escaped, they multiply into the surrounding matrix and form solid sprouts. These help connect the neighbouring blood vessels.
- The sprouts extend towards the source of the angiogenic stimulus. The new endothelial cells use adhesion molecules like integrins that help them bind to each other to form chains. These sprouts then form loops to become tubular blood vessels.
- Sprouting may occur rapidly at a rate of several millimeters per day.
Intussusceptive angiogenesis or splitting angiogenesis
This type of angiogenesis basically involves splitting or breaking down of a larger blood vessel into smaller ones. The blood vessel or capillary wall enters the existing lumen of the blood vessel to break it up into two or more smaller blood vessels.
Intussusception allows a large increase in the number of capillaries without a corresponding increase in the number of endothelial cells. This is important in development of the embryo.
This occurs in several phases that include:-
- The capillary walls facing each other come in contact at a point.
- Then the endothelial cell junctions are altered so that a bilayer of blood vessel walls is formed.
- This bilayer is then perforated by angiogenesis factor activated endothelial cells. This allows growth factors and cells to penetrate into the lumen.
- A core is formed at the point of contact between the walls. This is filled up with pericytes and myofibroblasts.
- The new cells begin forming the collagen fibres in the core and help provide an extracellular matrix for growth of the vessel lumen.
- The core then splits the existing blood vessel lumen into two.