The term angiogenesis encompasses all metabolic processes that involve the growth or new formation of blood vessels. Angiogenesis represents a complex process involving endothelial progenitor cells, smooth muscle cells, and pericytes. Promotion or inhibition of angiogenesis is increasingly used for therapeutic purposes-particularly in tumor therapy.
What is angiogenesis?
The term angiogenesis encompasses all metabolic processes that involve the growth or new formation of blood vessels. Angiogenesis in the narrow sense is used to refer only to the formation of new blood vessels as an extension of the existing vascular system, whereas the formation of blood vessels from progenitor cells, such as during embryonic development, is also referred to as vasculogenesis. In many cases, however, all processes leading to the formation of new blood and lymph vessels are grouped under the term angiogenesis. During embryonic development, omnipotent angioblasts form from the mesoderm at an early stage and can further develop into vascular endothelial cells for angiogenesis. Some of the angioblasts remain in the blood throughout life as undifferentiated hemangioblasts with stem cell potential. After the embryonic and growth phase, angiogenesis serves to expand the blood and lymphatic vascular system when necessary and, above all, to supply new tissue during wound healing. The body is even capable of forming replacement vessels for occluded or interrupted veins through angiogenesis. The formation of new vessels is mainly controlled by growth-promoting signaling hormones such as VEGF (vascular endothelial growth factor) and bFGF (basic fibroblast growth factor). Endothelial proliferation and migration, which are necessary in angiogenesis, require the excitations of the signaling hormone bFGF to initiate and control the process.
Function and task
Almost all tissues are connected to the body’s supply and disposal system. With few exceptions, the exchange of substances occurs in the capillaries of the bloodstream. In the capillaries surrounding the alveoli in the pulmonary circulation (also called the small circulation), the blood takes up molecular oxygen and releases carbon dioxide via diffusion processes. In the capillaries of the systemic circulation, the opposite exchange of substances takes place. The blood releases oxygen and other required substances to the tissues and absorbs carbon dioxide and other metabolic products. The blood circulation thus makes it possible for certain metabolic processes in the body to take place centrally in organs specialized for this purpose and for the metabolic products to be transported in the blood as far as desired. During embryonic development and the human growth phase, angiogenesis creates the conditions for the exchange of substances in the capillaries and the transport of substances within the body by forming a network of arteries, arterioles, capillaries, venules, veins and lymphatic vessels. The main task of angiogenesis is therefore to provide for the development and growth of the required network of many different types of blood and lymph vessels. After completion of the growth phase, angiogenesis is mainly useful as a repair mechanism for injured tissue. Disrupted veins need to be bridged or a new network needs to restore blood circulation. Angiogenesis also plays an important role in remodeling or rebuilding tissues in the body during the adult phase. Stimulation for local angiogenesis occurs via various messenger substances such as VEGF and bFGF, which can dock onto specific receptors in the blood vessels. In addition, fibroblast growth factors (FGF) play a role. A total of 23 different FGFs are known, each systematized with an atomic number from 1 to 23. They are single-chain polypeptides, i.e. chain molecules consisting of amino acids strung together. FGF-1 in particular, which consists of a chain of 141 amino acids and can therefore also be called a protein, has an important function in angiogenesis. It can dock to all FGF receptors and has a particularly activating effect on endothelial cell proliferation and migration.
Diseases and disorders
Related to diseases and disorders are both decreased angiogenesis and undesired angiogenesis. For example, it is what enables the growth of various types of tumors and their
metastasis.In pathological changes of the vascular system in local tissues, such as coronary heart disease (CHD) and peripheral occlusive disease (PAVD), e.g. a smoker’s leg, enhanced angiogenesis could lead to a replacement network of veins and at least partially restore the original function. Since the late 1990s, FGF-1, a fibroblast growth factor known to be potent, has been used clinically for the first time. FGFs have particular importance in the regeneration of nerve and cartilage tissue in addition to angiogenesis. The growth of certain tumors is determined by the efficiency of angiogenesis. Tumors are usually very energy-hungry and require a good network of specially created capillaries to supply and dispose of their cells. In tumors that tend to metastasize, the metastatic cells are distributed throughout the body via the blood. Since messenger substances such as FGFs, VEGF and bFGF also play a crucial role in angiogenesis in this case, therapy is aimed at inhibiting the messenger substances in order to stop the angiogenesis associated with the tumor tissue. At best, this would starve the tumor tissue and cause it to die. A first drug targeting the inhibition of the messenger VEGF was approved in Germany in 2005 and is mainly used in advanced colorectal cancer. In age-related macular degeneration (AMD), in which, in part, increased formation of new vessels with insufficient stability leads to gradual destruction of the photoreceptors, attempts are also being made to inhibit the undesirable process of angiogenesis at the retina by means of an anti-angiogenesis drug, thereby stopping the degradation of the photoreceptors in the macular region.
