Multifaceted role of vascular endothelial growth factor signaling in adult tissue physiology: An emerging concept with clinical implications

PURPOSE OF REVIEW: In addition to the crucial role of vascular endothelial growth factor (VEGF)A in vessel development, it has become apparent that the VEGF signaling pathway (VSP) plays an important role during adulthood in the maintenance of tissue homeostasis in normal physiological processes, as well as in pathological conditions. This review will focus on the role of the VSP for proper function of many organs in adult life. RECENT FINDINGS: Although adult angiogenesis is essentially quiescent-with the exception for wound healing and the menstrual cycle-manipulations of the VSP in mice have revealed its much broader and essential role in adult physiology and pathological conditions. Although suppression of the VSP is a promising clinical approach to treat cancer and age-related macular degeneration, it is associated with severe side effects. These adverse reactions caused by systemic VSP suppression in patients and the knowledge that has been gained from mouse models have contributed to our increasing understanding of the vast spectrum of functions that can be attributed to VEGF. SUMMARY: We will review the multifaceted role of VEGF signaling in adult life and highlight how genetic approaches have verified and explained the spectrum of side effects of antiangiogenic therapies using systemic modulation of the VSP. The fascinating parallels that become evident calls for the development of further animal models to address specific questions that could have implications in disease treatments targeting the VSP.