Vasculogenesis is a process of embryonic development in which the vascular system arises from endothelial progenitor cells. Vasculogenesis is followed by angiogenesis, which causes the first vessels to sprout into the bloodstream. In the broadest sense, cancer can be considered a vasculogenetic problem.
What is vasculogenesis?
Vasculogenesis is a process of embryonic development in which endothelial progenitor cells give rise to the vascular system. In medicine, vasculogenesis refers to the formation of blood vessels, for which endothelial progenitor cells serve as the starting material. These cells originate from the bone marrow and are attracted by messenger substances. These cytokines include, for example, vascular endothelial growth factor (VEGF ). After the messenger substances are released, the progenitor cells migrate from the bone marrow via the bloodstream to the site of the messenger substance. On the one hand, this process plays a role in wound healing and the associated formation of new vessels, and on the other hand, it may be due to pathological relationships such as tumors. In the meantime, medicine also assumes that vasculogenesis plays an increased role during embryonic development and that angiogenesis occurs almost exclusively in adult humans. This is considered to be the formation of new vessels by sprouting and cleavage processes, which uses pre-formed blood vessels as starting material. A third type of vessel formation is arteriogenesis, in which arteries and arterioles are formed by smooth muscle cell recruitment.
Function and purpose
The term vasculogenesis includes any type of new vessel formation from vascular endothelial or angioblast progenitor cells. Often, the term refers specifically to the new formation processes of vessels during embryonic development. These processes begin with the differentiation of mesodermal cells and continue with the assembly of these cells, which occurs in the region of the yolk sac and involves common progenitor cells from the vascular and hematopoietic systems. These progenitor cells are also known as hemangioblasts. The resulting cell conglomerates are called blood islands. Their differentiation occurs under the influence of growth factors. In particular, the influence of VEGF plays a role in this process. Differentiation turns the progenitor cells into marginal angioblasts and central hematopoietic stem cells. The angioblasts become endothelial cells and as such form the first vessels in humans. These processes are followed by processes of aniogenesis. The first blood vessels sprout during these processes and form the entire blood system by sprouting. As the primitive cells of the endothelium assemble and form intercellular contacts in this way, the process gives rise, after additional differentiation and growth processes, to the individual vascular compartments known as the intravascular space. The first vessels form in embryonic development as early as about day 18. These initial vessels correspond to the so-called umbilical vessels and include, in addition to the umbilical artery, the umbilical vein, from which all other vessels arise. After completion of embryonic development, vasculogenesis hardly occurs in the actual form. Vascular neogenesis in adult humans usually takes place either compensatorily, or corresponds to destructive processes. Unlike in embryonic development, new vessels in the adult organism are ultimately formed only on the basis of already existing vessels inform angiogenesis. This new formation remains predominantly limited to processes of wound healing. Like pathological and uncontrolled new vessel formation in the context of tumor diseases, physiological new formation after injury or in transplantation medicine is sometimes subsumed under the term neovascularization. Although this term is related to vasculogenesis, it should not be considered a synonym.
Diseases and disorders
In the context of vasculogenesis, vascular endothelial growth factor (VEGF) plays a major role. This growth factor also has the highest clinical relevance when it comes to processes of vesculogenesis. The substance is a signaling molecule that drives vasculogenesis and subsequent angiogenesis. The growth factor stimulates the endothelium and shows effects on monocytes and macrophages migrating through the substance.In vitro, VEGF provides a stimulatory effect on endothelial cell division and immigration. Increased expression of VEGF-A is associated with some tumors in clinical practice. The monoclonal antibody bevacizumab can bind to VEGF and inhibit pathological vascularization in this way. Bevacizumab therefore plays a role in the therapy of various types of cancer. Phase III studies have successfully used the substance to combat colorectal cancer, lung cancer or breast cancer. Phase II trials also exist for the treatment of cancers such as pancreatic cancer, prostate cancer or kidney cancer. Ranibizumab is known as a fragment of the same antibody. This substance is used therapeutically when macular degeneration is associated with vascular neoplasms. In addition, tyrosine kinase inhibitors such as sunitinib or vatalanib, which have an inhibitory effect on VEGF receptors, are now also used against diseases such as cancer. The fact that cancer in particular is related to vasculogenesis has a simple reason. Above a certain size, a tumor needs its own vascular system. Only in this way can it be adequately supplied with nutrients and oxygen and grow in size. Therefore, if the oxygen and nutrient supply is blocked by an interruption of the vasculogenetic processes, the tumor will stop growing. However, activation of vasculogenesis can also be relevant for medicine. This is especially true after transplantation. It is the connection of grafts to the vascular system that secures their oxygen and nutrient supply and allows transplantation to succeed.
