Angiogenesis occurs as a result of cells sensing local levels of oxygen, and determining them as being lower than the required concentration for the body to maintain a certain level physical rigour. The tissue is described as being hypoxic, and responds with the release of factors to promote vessel growth. As a result, tissues with insufficient blood supply, and hence oxygen supply, can promote capillary growth towards them within a few hours of becoming hypoxic. This ensures that almost all metabolically active cells are within range of a few hundred micrometres away from a blood capillary at any one time. New capillary formation occurs as a result of a balance of inducers and inhibitors of the process of angiogenesis.
In order to promote new vessel growth, the oxygen starved tissues secrete large quantities of angiogenic factors which include the secreted protein –vascular endothelial growth factor- VEGF. These proteins bind to capillaries and this results in their branching. The endothelial cells are important as they are the cells activated by VEGF, and upon activation, become highly mobile. They transition from the parent vessel towards the source of VEGF. They also release enzymes which are called proteases that hydrolyse surrounding proteins, clearing a path for new vessel growth. The movement of endothelial cells is highly coordinated, and areas exposed to the highest concentration of VEGF lead the branching and are referred to as tip cells. The endothelial cells which encounter low concentrations of VEGF are stalk cells, which trail tip cells during blood vessel sprouting. Stalk cells are less motile than tip cells and maintain connections with the original parent vessel. The differences between the behaviour of the two cells are important. They ensure endothelial cells migrate in an ordered fashion.
Upon contact being made between a branching vessel with another, they fuse to form a new continuous vessel. The oxygenation of the target tissue afterwards, by the blood flowing through the newly formed capillary, switches off the release of pro-angiogenic factors, including VEGF, and returns the system to its norm, by flipping the balance to favour angiogenesis inhibitors.
It is in periods of rigorous exercise that blood vessel growth becomes more prevalent as a result of an increase in skeletal muscle movement, which of course results in a higher demand for oxygen to maintain the level of physical activity, thus resulting in hypoxia. It is for this very reason that exercise has such highly regarded benefits, as it not only delivers a vast amount of oxygen and nutrients to your tissues, whilst increasing the efficiency of your cardiovascular system, but it also promote angiogenesis, which is vital for healing, and vessel regeneration.
- Philip Alan, Blood Vessels Biological sciences Review, Feb 2017