###### Created: 2024-01-12 16:39 ###### Areas & Topics: #medicine #embryology #physiology ###### Note Type: #permanent ###### Connected to: [[]] - Angiogenesis is the process of new blood vessels forming from pre-existing blood vessels. - It is a normal physiological process seen in both embryology (following [[Vasculogenesis]]) and adulthood. - It is also the main reason for blood vessel growth throughout most of development and in most pathology. - There are three different types of angiogenesis. ### Sprouting Angiogenesis - Sprouting angiogenesis is a form of angiogenesis that is characterised by new vessels being formed by sprouting off pre-existing vessels and is the most well understood. It has several stages which occur as follows: 1) Areas of tissue which have no vasculature and are therefore hypoxic demand nutrients and oxygen. 2) This stimulates parenchymal cells in these tissues to release vascular endothelial growth factor (VEGF-A). 3) The VEGF-A stimulates receptors on endothelial cells in pre-existing blood vessels and activates these cells. 4) These now activated endothelial cells, also known as tip cells, release proteases (enzymes). 5) These proteases break down the basement membranes of the pre-existing blood vessel, allowing endothelial cells to leak through and proliferate to form sprouts from the main vessel (these proliferating cells are known as stalk cells). 7) These new sprouts go towards the source of the angiogenic stimulus (i.e. the areas producing VEGF-A and other substances) and form loops to begin fully forming the lumens of new blood vessels. 8) As this happens, endothelial cells also migrate simultaneously and adhere to the other cells using integrins (adhesion molecules) to further form the new blood vessels. 9) This sprouting allows new vessels to form and bridge gaps between pre-existing vasculature. ### Intussusceptive Angiogenesis (Splitting Angiogenesis) - Intussusceptive angiogenesis is where a new blood vessel is formed by an old blood vessel being split into two. - This process is important because it allows new blood vessels and capillary networks to form by reorganising pre-existing cells, instead of requiring the formation of completely new ones. - This means bigger capillary networks can be made without requiring as many resources (especially important during embryological development). Stage 1 - Contact: - Two opposing capillary walls (i.e. the wall on each side of one capillary) establish a zone of contact with one another (i.e. touch within the vessel lumen) Stage 2 - Perforation: - The endothelial cell junctions on each wall near this zone of contact are reorganised, allowing the vessel bilayer which has been created to be perforated so cells and growth factors can leak through. - These cells and growth factors can then perforate into the lumen of the capillary. Stage 3 - Core Formation: - The new space created in this zone of contact is filled with pericytes and myofibroblasts to form a core, by laying down collagen to provide an extracellular matrix for the new vessel lumens to grow into. - This creates a bifurcation of the capillary, thereby making a new capillary from the existing one. Stage 4 - Fleshing: - The core is then fleshed out without alterations to the basic structure of the capillaries. ![[Mechanisms-of-angiogenesis-sprouting-A-vs-intussusception-or-splitting-B-A-VEGF.jpg]] ### Coalescent Angiogenesis - This type of angiogenesis is thought of as the opposite of intussusceptive angiogenesis, and is characterised by the coalescing (fusing) of two capillaries to form a larger vessel. - It has recently been thought to not only be part of embryological development, but also tumour formation. ### Resources https://en.wikipedia.org/wiki/Angiogenesis https://en.wikipedia.org/wiki/Intussusceptive_angiogenesis