Angiogenesis in development, disease, and regeneration

Abstract

The cardio-vascular system consists of the heart, arterial networks, capillary plexuses, and venous networks (www.le.ac.uk/pa/teach/va/anatomy/case1/ frmst.html, http://www.angio.org/). Working in parallel with the blood circulation is the lymphatic system that drains interstitial fluid from tissue and returns it back into the venous blood circulation. The circulatory systems arose during evolution to provide transport routes for supplying nutrients, soluble factors and gaseous molecules, and removing waste products and metabolic intermediates from different tissues in the body. These functions are required to maintain homeostasis. When the circulatory system goes awry, it can result in a number of different diseases. For example, when circulation is partially or completely disrupted, or when vessels become structurally or functionally abnormal, the affected tissue rapidly undergoes a number of physiological changes related to the drop in tissue oxygenation (hypoxia). This state is defined as ischemia and can become pathological when hypoxic conditions persist. Ischemia induces cellular dysfunctions that thwart the normal function of the tissue, and depending on the tissue type and severity of ischemia, irreversible damage including cell death may occur. Ischemia can occur in any tissue, but its effects on the heart lead to the highest morbidity andmortality because it directly affects the circulatory system. Once a tissue suffers from injury, it may either undergo healing with scar formation or it may regenerate and regain partial or complete normal function. Therapeutic angiogenesis aims to promote the regeneration of the injured tissue by creating a favorable environment with a rich blood supply for repair. Pathological states are induced not only by blood vessel disruption or aberrant function, but can also result from blood vessel formation in tissues that are normally avascular (e.g., retina in macula degeneration and cartilage in arthritis) or in newly formed tissues (e.g., tumors or atherosclerotic plaques). Thus, the challenge for therapy in these diseases will be to discover strategies to judiciously promote or halt the formation of new blood vessels, depending on the type of vascular disease. We discuss in this chapter the process of angiogenesis during development and in physiological and pathological settings.We will then cover some of the main molecular pathways involved in angiogenesis and review the tools and techniques that are currently used to study new vessel formation. Finally, we will discuss the concept and application of angiogenic or anti-angiogenic therapy in regenerative medicine. © Springer Science+Business Media, LLC 2009.