Editing Angiogenesis (section)

====VEGF====
[[Vascular endothelial growth factor]] (VEGF) has been demonstrated to be a major contributor to angiogenesis, increasing the number of capillaries in a given network. Initial ''in vitro'' studies demonstrated bovine capillary endothelial cells will proliferate and show signs of tube structures upon stimulation by VEGF and [[bFGF]], although the results were more pronounced with VEGF.<ref name="Goto1993">{{cite journal | vauthors = Goto F, Goto K, Weindel K, Folkman J | title = Synergistic effects of vascular endothelial growth factor and basic fibroblast growth factor on the proliferation and cord formation of bovine capillary endothelial cells within collagen gels | journal = Laboratory Investigation; A Journal of Technical Methods and Pathology | volume = 69 | issue = 5 | pages = 508–517 | date = November 1993 | pmid = 8246443 }}</ref> Upregulation of VEGF is a major component of the physiological response to exercise and its role in angiogenesis is suspected to be a possible treatment in vascular injuries.<ref name="Ding2004">{{cite journal | vauthors = Ding YH, Luan XD, Li J, Rafols JA, Guthinkonda M, Diaz FG, Ding Y | title = Exercise-induced overexpression of angiogenic factors and reduction of ischemia/reperfusion injury in stroke | journal = Current Neurovascular Research | volume = 1 | issue = 5 | pages = 411–420 | date = December 2004 | pmid = 16181089 | doi = 10.2174/1567202043361875 | url = http://www.bentham-direct.org/pages/content.php?CNR/2004/00000001/00000005/003AG.SGM | url-status = usurped | s2cid = 22015361 | archive-url = https://web.archive.org/web/20120419004150/http://www.bentham-direct.org/pages/content.php?CNR%2F2004%2F00000001%2F00000005%2F003AG.SGM | archive-date = April 19, 2012 | url-access = subscription }}</ref><ref name="Gavin2004">{{cite journal | vauthors = Gavin TP, Robinson CB, Yeager RC, England JA, Nifong LW, Hickner RC | title = Angiogenic growth factor response to acute systemic exercise in human skeletal muscle | journal = Journal of Applied Physiology | volume = 96 | issue = 1 | pages = 19–24 | date = January 2004 | pmid = 12949011 | doi = 10.1152/japplphysiol.00748.2003 | s2cid = 12750224 }}</ref><ref name="Kraus2004">{{cite journal | vauthors = Kraus RM, Stallings HW, Yeager RC, Gavin TP | title = Circulating plasma VEGF response to exercise in sedentary and endurance-trained men | journal = Journal of Applied Physiology | volume = 96 | issue = 4 | pages = 1445–1450 | date = April 2004 | pmid = 14660505 | doi = 10.1152/japplphysiol.01031.2003 | s2cid = 21090407 }}</ref><ref name="Lloyd2003">{{cite journal | vauthors = Lloyd PG, Prior BM, Yang HT, Terjung RL | title = Angiogenic growth factor expression in rat skeletal muscle in response to exercise training | journal = American Journal of Physiology. Heart and Circulatory Physiology | volume = 284 | issue = 5 | pages = H1668–H1678 | date = May 2003 | pmid = 12543634 | doi = 10.1152/ajpheart.00743.2002 }}</ref> ''In vitro'' studies clearly demonstrate that VEGF is a potent stimulator of angiogenesis because, in the presence of this growth factor, plated endothelial cells will proliferate and migrate, eventually forming tube structures resembling capillaries.<ref name="Prior2004" />
VEGF causes a massive signaling cascade in [[endothelium|endothelial]] cells. Binding to VEGF receptor-2 (VEGFR-2) starts a tyrosine kinase signaling cascade that stimulates the production of factors that variously stimulate vessel permeability (eNOS, producing NO), proliferation/survival (bFGF), migration (ICAMs/VCAMs/MMPs) and finally differentiation into mature blood vessels. Mechanically, VEGF is upregulated with muscle contractions as a result of increased blood flow to affected areas. The increased flow also causes a large increase in the [[mRNA]] production of VEGF receptors 1 and 2. The increase in receptor production means muscle contractions could cause upregulation of the signaling cascade relating to angiogenesis. As part of the angiogenic signaling cascade, NO is widely considered to be a major contributor to the angiogenic response because inhibition of NO significantly reduces the effects of angiogenic growth factors. However, inhibition of NO during exercise does not inhibit angiogenesis, indicating there are other factors involved in the angiogenic response.<ref name="Prior2004" />