Angiogenesis is the formation of new blood vessels from pre-existing ones. This process of generating new capillaries begins before birth and continues throughout life. All tissues depend on the diffusion of nutrients and metabolites from nearby capillaries. To visualize this, one can imagine the body’s vascular system as a network of highways, with angiogenesis being the construction of new local roads branching off to service new developments.
This biological function is responsible for most blood vessel growth during development and in disease. The process is highly regulated under normal conditions. When tissues are not receiving enough oxygen, a condition known as hypoxia, cells send out chemical signals that initiate angiogenesis. This mechanism supplies tissues with the necessary oxygen and nutrients to grow and heal.
The Biological Process of Angiogenesis
The process of angiogenesis unfolds through coordinated steps, driven by a balance of chemical signals. When a tissue requires a new blood supply, it releases pro-angiogenic signaling molecules. The most prominent of these is Vascular Endothelial Growth Factor (VEGF), which acts as a primary “go” signal. These signals travel to the endothelial cells, the specialized cells that form the inner lining of existing blood vessels.
Upon receiving these signals, the endothelial cells are activated. They produce enzymes that break down the extracellular matrix, the scaffold-like structure that surrounds the blood vessel. This allows the endothelial cells to migrate from the parent vessel toward the source of the angiogenic stimulus. Following this migration, the cells proliferate to form a solid sprout.
This initial sprout then hollows out to create a new tube, which connects with other vessels to establish blood flow. This process is known as sprouting angiogenesis. Another form, intussusceptive angiogenesis, involves the splitting of existing vessels to increase the density of capillaries within a tissue.
Angiogenesis in Health and Healing
Angiogenesis is a normal and beneficial process, from initial development to adult tissue repair. During embryonic development, it is responsible for establishing the complete vascular system. This allows the growing fetus to receive the oxygen and nutrients necessary for organ formation.
In adults, angiogenesis is apparent during wound healing. When an injury occurs, the body initiates angiogenesis to form new blood vessels that grow into the damaged area. These new capillaries deliver oxygen, nutrients, and immune cells to the site to clear debris and rebuild the tissue. This restoration of blood supply is part of how the body naturally repairs itself.
The female reproductive cycle also relies on the regulated growth of new blood vessels. For instance, the lining of the uterus, the endometrium, undergoes monthly cycles of growth that require angiogenesis to build up the tissue for potential pregnancy. Similarly, the formation of the placenta during pregnancy is an angiogenic event, ensuring the fetus has a robust connection to the maternal blood supply.
The Role of Angiogenesis in Disease
While angiogenesis is a normal bodily process, it can be exploited by diseases when its regulation is disrupted. Uncontrolled angiogenesis is a hallmark of cancer. Tumors require a supply of oxygen and nutrients to grow beyond a very small size. To secure this, cancer cells secrete large quantities of angiogenic growth factors, such as VEGF, which stimulate nearby blood vessels to grow into the tumor mass.
These new tumor blood vessels are often abnormal, with irregular shapes and leaky walls. This network not only feeds the primary tumor, allowing it to expand, but also provides a pathway for cancer cells to enter the bloodstream. This process, known as metastasis, allows the cancer to spread to distant parts of the body.
Beyond cancer, excessive angiogenesis contributes to other diseases. In wet age-related macular degeneration (AMD), abnormal and leaky blood vessels grow in the retina, leading to vision loss. In diabetic retinopathy, another leading cause of blindness, new, fragile blood vessels form in the retina, which can leak and cause damage. Conditions like rheumatoid arthritis and psoriasis also involve overactive angiogenesis, which fuels chronic inflammation.
Therapeutic Control of Angiogenesis
Medical interventions have been developed to manipulate angiogenesis, either by inhibiting it or promoting it, depending on the disease. Anti-angiogenic therapies are a component of modern cancer treatment. These treatments work by interfering with the signals that stimulate new blood vessel growth, effectively aiming to cut off a tumor’s blood supply and starve it of nutrients.
A common class of these drugs includes monoclonal antibodies, such as bevacizumab, which specifically target and block VEGF. Another approach involves tyrosine kinase inhibitors like sunitinib and sorafenib, which block the receptors on endothelial cells that VEGF would normally bind to. While these therapies can be effective, some tumors develop resistance over time by finding alternative pathways to stimulate blood vessel growth.
Conversely, pro-angiogenic therapies are being explored for conditions where insufficient blood vessel growth is the problem. In cases of coronary artery disease or chronic wounds like diabetic foot ulcers, stimulating the growth of new vessels could help restore blood flow to oxygen-deprived tissues. This approach, known as therapeutic angiogenesis, aims to accelerate healing and repair tissues that have been damaged by a lack of circulation.