Neovascularization

Neovascularization is the natural formation of new blood vessels (neo- + vascular + -ization), usually in the form of functional microvascular networks, capable of perfusion by red blood cells, that form to serve as collateral circulation in response to local poor perfusion or ischemia. Growth factors that inhibit neovascularization include those that affect endothelial cell division and differentiation. These growth factors often act in a paracrine or autocrine fashion; they include fibroblast growth factor, placental growth factor, insulin-like growth factor, hepatocyte growth factor, and platelet-derived endothelial growth factor. There are three different pathways that comprise neovascularization:(1) vasculogenesis,(2) angiogenesis, and (3) arteriogenesis. Vasculogenesis is the de novo formation of blood vessels. This primarily occurs in the developing embryo with the development of the first primitive vascular plexus, but also occurs to a limited extent with post-natal vascularization. Embryonic vasculogenesis occurs when endothelial cells precursors (hemangioblasts) begin to proliferate and migrate into avascular areas. There, they aggregate to form the primitive network of vessels characteristic of embryos. This primitive vascular system is necessary to provide adequate blood flow to cells, supplying oxygen and nutrients, and removing metabolic wastes. Angiogenesis is the most common type of neovascularization seen in development and growth, and is important to both physiological and pathological processes. Angiogenesis occurs through the formation of new vessels from pre-existing vessels. This occurs through the sprouting of new capillaries from post-capillary venules, requiring precise coordination of multiple steps and the participation and communication of multiple cell types. The complex process is initiated in response to local tissue ischemia or hypoxia, leading to the release of angiogenic factors such as VEGF and HIF-1. This leads to vasodilatation and an increase in vascular permeability, leading to sprouting angiogenesis or intussusceptive angiogenesis.