Editing Angiogenesis (section)

==Types==

===Sprouting angiogenesis===
Sprouting angiogenesis was the first identified form of angiogenesis and because of this, it is much more understood than intussusceptive angiogenesis. It occurs in several well-characterized stages. The initial signal comes from tissue areas that are devoid of vasculature. The [[Hypoxia (medical)|hypoxia]] that is noted in these areas causes the tissues to demand the presence of nutrients and oxygen that will allow the tissue to carry out metabolic activities. Because of this, parenchymal cells will secrete vascular endothelial growth factor ([[VEGF-A]]) which is a proangiogenic growth factor.<ref>Adair TH, Montani JP. Angiogenesis. San Rafael (CA): Morgan & Claypool Life Sciences; 2010. Chapter 1, Overview of Angiogenesis. Available from: https://www.ncbi.nlm.nih.gov/books/NBK53238/</ref>  These biological signals activate [[receptor (biochemistry)|receptor]]s on [[endothelial cell]]s present in pre-existing blood vessels.  Second, the activated endothelial cells, also known as '''tip cells''',<ref name="Weavers">{{cite journal | vauthors = Weavers H, Skaer H | title = Tip cells: master regulators of tubulogenesis? | journal = Seminars in Cell & Developmental Biology | volume = 31 | issue = 100 | pages = 91–99 | date = July 2014 | pmid = 24721475 | pmc = 4071413 | doi = 10.1016/j.semcdb.2014.04.009 }}</ref> begin to release [[enzyme]]s called [[protease]]s that degrade the [[basement membrane]] to allow endothelial cells to escape from the original (parent) vessel walls. The [[endothelial cell]]s then [[cell growth|proliferate]] into the surrounding [[Matrix (biology)|matrix]] and form solid sprouts connecting neighboring vessels. The cells that are proliferating are located behind the tip cells and are known as '''stalk cells'''.<ref name="Weavers"/> The proliferation of these cells allows the capillary sprout to grow in length simultaneously.

As sprouts extend toward the source of the angiogenic stimulus, endothelial cells migrate in [[tandem]], using adhesion molecules called [[integrin]]s.  These sprouts then form loops to become a full-fledged vessel [[lumen (anatomy)|lumen]] as cells migrate to the site of angiogenesis. Sprouting occurs at a rate of several millimeters per day, and enables new vessels to grow across gaps in the [[vasculature]]. It is markedly different from splitting angiogenesis because it forms entirely new vessels as opposed to splitting existing vessels.

===Intussusceptive angiogenesis===
{{main|Intussusceptive angiogenesis}}
[[Intussusceptive angiogenesis]], also known as ''splitting angiogenesis'', is the formation of a new blood vessel by splitting an existing blood vessel into two.

Intussusception was first observed in [[neonatal]] rats. In this type of vessel formation, the capillary wall extends into the [[lumen (anatomy)|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 junction]]s 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 [[pericyte]]s and [[myofibroblast]]s. 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 cell]]s. This is especially important in embryonic development as there are not enough resources to create a rich [[Microcirculation|microvasculature]] with new cells every time a new vessel develops.<ref name="Burri2004">{{cite journal | vauthors = Burri PH, Hlushchuk R, Djonov V | title = Intussusceptive angiogenesis: its emergence, its characteristics, and its significance | journal = Developmental Dynamics | volume = 231 | issue = 3 | pages = 474–488 | date = November 2004 | pmid = 15376313 | doi = 10.1002/dvdy.20184 | s2cid = 35018922 | doi-access = free }}</ref>

===Coalescent angiogenesis===
{{main|Coalescent angiogenesis}}
[[Coalescent angiogenesis]] is a mode of angiogenesis, considered to be the opposite of intussusceptive angiogenesis, where capillaries fuse, or coalesce, to make a larger bloodvessel, thereby increasing blood flow and circulation.<ref name="pmid34905124">{{cite journal | vauthors = Nitzsche B, Rong WW, Goede A, Hoffmann B, Scarpa F, Kuebler WM, Secomb TW, Pries AR | display-authors = 6 | title = Coalescent angiogenesis-evidence for a novel concept of vascular network maturation | journal = Angiogenesis | volume = 25 | issue = 1 | pages = 35–45 | date = February 2022 | pmid = 34905124 | pmc = 8669669 | doi = 10.1007/s10456-021-09824-3 }}</ref> Coalescent angiogenesis has extended out of the domain of embryology. It is assumed to play a role in the formation of neovasculature, such as in a tumor.<ref name="pmid34993716">{{cite journal | vauthors = Pezzella F, Kerbel RS | title = On coalescent angiogenesis and the remarkable flexibility of blood vessels | journal = Angiogenesis | volume = 25 | issue = 1 | pages = 1–3 | date = February 2022 | pmid = 34993716 | doi = 10.1007/s10456-021-09825-2 | s2cid = 254188870 | doi-access = free }}</ref>