Neovascularization: Function, Role & Diseases

All processes of new vessel formation that take place in the organism of an adult human are summarized as vascularization, most notably angiogenesis. Neovascularization, on the other hand, is more commonly known as pathological and thus pathologically excessive new formation of vessels. This neovascularization occurs, for example, in the context of cancer and serves to supply tumors with nutrients and oxygen.

What is neovascularization?

Neovascularization is more commonly known as pathological and thus pathologically excessive new formation of vessels. This neovascularization occurs, for example, in the context of cancer and serves to supply tumors with nutrients and oxygen. In the course of the so-called vascularization, smaller blood vessels are newly formed. Vascularized tissues therefore carry a particularly large number of blood vessels and bleed much more profusely after injuries, which benefits wound healing. Physiological processes of new vessel formation are summarized under the technical term angiogenesis. In angiogenesis, new blood vessels grow from existing blood vessels in cleavage and sprouting processes, for example to bypass constrictions. In addition to shear forces in the vessels, these processes depend primarily on the blood concentration of immunological monocytes. Vascularization can be used synonymously with angiogenesis or refers to the overall blood supply to a tissue or organ. Neovascularization is used as a generic term for all new vessel formation in an adult organism. Since in the adult organism, apart from wound healing, vascular neovascularization is usually associated with pathological manifestations, the term neovascularization is usually also the title of a disease. In this context, neovascularization is always present when an angiogenic process is not a physiological but a pathological process. Accordingly, mainly excessive vascular neoplasms in the context of tumor diseases or macular degeneration are titled as neovascularization. Physiologic vascular neovascularization in the adult organism is referred to as vascularization rather than neovascularization, although it is indeed neovascularization.

Function and Purpose

Angiogenesis involves the formation of new vascular structures with endothelial cell linings and smooth muscle cells and pericytes. Angiogenesis is a process of wound healing that should not be underestimated. The blood supplies all body tissues and organs in humans with nutrients and oxygen. In addition, messenger substances reach the individual tissues via the blood. In addition, the cells of the immune system are also transported via the blood. Thus, the blood connection of a tissue is vital. In this context, angiogenesis ensures the survival of tissues whose blood connection has been disrupted due to injury. Together with the term vascularization, the term angiogenesis has now established itself as an umbrella term for all forms of new vessel formation in the adult organism. In addition to the wound healing process described above, there is, for example, vasculogenesis, in which vascular structures are newly formed on the basis of circulating stem cells or angioblasts that become endothelial cells. In arteriogenesis, arteries and smaller arterioles form again and acquire full vessel walls by means of smooth muscle cell recruitment. Essentially the same process occurs in the formation of new veins. All of the aforementioned new vessel formations are vascularizations and are sometimes based on a release of the growth factor VEGF. In neovascularization, a locally limited overproduction of VEGF occurs. This overproduction may be due, for example, to release by tumor cells. In progressive tumor disease, tumor cells initiate neovascularization so that the growing, progressively spreading tumor is adequately supplied with blood and thus receives sufficient oxygen and nutrients to grow. In this context, blocking neovascularization can halt tumor growth. This principle is used in anti-angiogenic tumor therapy to treat patients with cancer.

Diseases and disorders

Neovascularization occurs in the setting of numerous tumor diseases. However, excessive vascularization with excessive production of VEGF is not always necessarily associated with a tumor.Especially in the case of vascular neoplasms in the eye, many other pathological processes may be to blame for the excessive vascularization. For example, exudative “wet” macular degeneration or diabetic retinopathy, also known as proliferative retinopathy. In addition, neovascularization plays out in the context of neovascularization glaucoma and also occurs concomitantly with retinopathy praematurorum. Neovascularization of the cornea is also frequently observed in patients wearing contact lenses. Depending on the cause, pathological excessive processes of vascularization are treated differently. To attenuate angiogenesis, anti-angiogenic therapy is usually given, for example, VEGF-neutralizing monoclonal antibodies. Treatment with bevacizumab or rhuMAb-VEGF, for example, has been approved for patients with metastatic colorectal cancer and is intended to block the formation of new blood vessels, which ultimately also blocks the growth of the tumor. The active ingredient bevacizumab is now also used in breast cancer, kidney cancer and lung cancer. In addition, anti-angiogenic therapies now exist with the antibody ramucirumab, which binds to the receptor VEGF R2 and in this way blocks the receptor for the angiogenic growth factor VEGF R2. The blockade prevents the formation of blood vessels, since the formation is only stimulated by the receptor-growth factor complex, which now no longer occurs. To date, ramucirumab has been used primarily in the treatment of gastric cancer. The situation is different for the therapy of excessive vascular neovascularization that is not associated with tumor diseases. In the case of neovascularization associated with contact lens use, discontinuation of contact lens use is the focus of therapy. Additionally, topical medications are used to regulate angiogenesis. These medications are usually eye drops. The active ingredients used are mainly steroids and GS-101. The latter substance is an antisense oligonucleotide.