Figure 2

The process of angiogenesis. A) Sprouting angiogenesis: formation of blood vessels is a multi-step process, which includes (i) reception of angiogenic signals (yellow spot) from the surrounding by endothelial cells (EC); (ii) retraction of pericytes from the abluminal surface of capillary and secretion of protease from activated endothelial cells (aEC) and proteolytic degradation of extracellular membrane (green dash-line); (iii) chemotactic migration of EC under the induction of angiogenic stimulators; (iv) proliferation of EC and formation of lumen/canalisation by fusion of formed vessels with formation of tight junctions; (v) recruitment of pericytes and deposition of new basement membrane and initiation of blood flow. B) Non-sprouting angiogenesis – intussusceptive microvascular growth: it is initiated by (i) protrusion of opposing capillary walls towards the lumen; (ii) perforation of the EC bilayer and formation of many transcapillaries with interstitial core (red arrow); (iii) formation of the vascular tree from intussusceptive pillar formation and pillar fusion and elongation of capillaries (green arrows).