Editing Angiogenesis (section)

===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.