Normal tissue function in mammals depends on adequate supply of oxygen. Alterations in oxygen homeostasis are caused by augmented oxygen consumption or a compromised oxygen delivery resulting in tissue hypoxia. Examples for changes in consumption include increases in muscle workload or increased neuronal activity, an example for the latter maybe the narrowing and occlusion of blood vessels as a result of atherosclerosis [1]. Thus, tissue oxygenation and finally cell survival is not only influenced by the metabolic activity of the tissue but equally well by the vascular system that feeds oxygen and nutrients to the respiring tissue. Therefore, the central role of the vascular system for proper organ function becomes immediately apparent, in that the vascular system must be able to adapt to physiologically altered metabolic demands within a given tissue area. For example, rats housed in complex environments as compared to animals kept in standard cages generate more new synaptic connections. This neuronal plasticity promotes capillary formation by generating long-lasting increases in metabolic demand [2]. These results indicate the existence of inherent self-adapting mechanisms that link metabolic demand to vascular oxygen supply and thus angiogenesis. To understand these adaptive responses, an in depth characterization of the mechanisms that control vascular morphogenesis is needed. These also have far-reaching clinical implications, as many pathological conditions such as tumor growth, ischemic diseases or blindness are associated with an unbalanced blood vessel formation.

During recent years it has emerged that oxygen availability affects several aspects of vascular morphogenesis. The identification of hypoxia-inducible angiogenic factors such as vascular endothelial growth factor (VEGF) and the subsequent discovery of the hypoxia-inducible transcription factors HIF-1 and HIF-2 which control oxygen-dependent gene expression has broadened our understanding of the molecular events that govern oxygen-dependent vessel growth.