During development, vascular endothelial growth factor (VEGF, also known as VEGFA) is essential for vasculogenesis and angiogenesis. Although VEGF is known to have roles in some pathological and physiological processes, its functions in adult organisms are less well understood. The fact that this growth factor is expressed in almost all adult tissues suggests that it is also required during adult vascular system homeostasis. But how is VEGF expression in the vascular system regulated and what processes does it initiate? Patricia D'Amore and colleagues (p. ) now provide an answer by showing that shear stress within the vasculature leads to VEGF expression and prolonged endothelial cell survival. The authors report that VEGF is expressed in arterial, but not venous or capillary, endothelial cells in vivo. In addition, they find that exposing human umbilical vein endothelial cells (HUVECs) to fluid shear stress upregulates VEGF expression and results in increased expression and activation of the VEGF receptor 2. An siRNA-based approach reveals that these effects are mediated through the transcription factor Krüppel-like factor 2 (KLF2). The increase in paracrine–autocrine VEGF signalling reduces the levels of endothelial cell apoptosis, which highlights a new mechanism through which shear stress in the adult arterial vasculature initiates pro-survival signals.
