Angiogenesis--a self-adapting principle in hypoxia.
Normal tissue function depends on adequate supply of oxygen through blood vessels. Reduced oxygen supply (hypoxia) induces a variety of specific adaptation mechanisms in mammals that occur at the cellular, local and systemic level. These mechanisms are in part governed by the activation of the hypoxia-inducible transcription factors HIF-1 and HIF-2. Prolyl and asparaginyl hydroxylases as recently characterized oxygen sensors allow the regulation of HIFs that in turn modulate expression of hypoxically regulated genes such as VEGF. VEGF plays a key role in the formation of a functional and integrated vascular network required during physiological processes such as embryogenesis or female reproductive cycle as well as during a variety of pathological processes such tumor growth, wound healing, retinopathy and ischemic diseases (myocardial infarction, cerebral ischemia). However, other angiogenic factors, such as angiopoietins, PDGF, ephrins and erythropoietin are additionally needed to enable the formation of a functional vascular network. Many of these factors are activated during hypoxia although no HIF binding sites have yet been identified in the regulatory sequences of theses genes. Hypoxia-induced gene products that result in new vessel growth may be part of a self-regulated physiological protection mechanism preventing cell injury, especially under conditions of chronically reduced blood blow (chronic ischemia).
Marti
Hugo H
HH
Institute of Physiology and Pathophysiology, University of Heidelberg, Im Neuenheimer Feld 326, D-69120 Heidelberg, Germany. hugo.marti@pio1.uni-heidelberg.de
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D008322:Mammals; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010101:Oxygen Consumption; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A