<P> By intussusception, also known as splitting angiogenesis, a new blood vessel is created by splitting of an existing blood vessel in two . </P> <P> Intussusception was first observed in neonatal rats . In this type of vessel formation, the capillary wall extends into the lumen to split a single vessel in two . There are four phases of intussusceptive angiogenesis . First, the two opposing capillary walls establish a zone of contact . Second, the endothelial cell junctions are reorganized and the vessel bilayer is perforated to allow growth factors and cells to penetrate into the lumen . Third, a core is formed between the 2 new vessels at the zone of contact that is filled with pericytes and myofibroblasts . These cells begin laying collagen fibers into the core to provide an extracellular matrix for growth of the vessel lumen . Finally, the core is fleshed out with no alterations to the basic structure . Intussusception is important because it is a reorganization of existing cells . It allows a vast increase in the number of capillaries without a corresponding increase in the number of endothelial cells . This is especially important in embryonic development as there are not enough resources to create a rich microvasculature with new cells every time a new vessel develops . </P> <P> Mechanical stimulation of angiogenesis is not well characterized . There is a significant amount of controversy with regard to shear stress acting on capillaries to cause angiogenesis, although current knowledge suggests that increased muscle contractions may increase angiogenesis . This may be due to an increase in the production of nitric oxide during exercise . Nitric oxide results in vasodilation of blood vessels . </P> <P> Chemical stimulation of angiogenesis is performed by various angiogenic proteins, including several growth factors . </P>

What stimulates the growth of new blood vessels