MicroRNA Control of Vascular Endothelial Growth Factor Signaling Output During Vascular Development

The regulated response of endothelial cells to signals in their environment is not only critical for the de novo formation of primordial vascular networks during early development (ie, vasculogenesis), but is also required for the subsequent growth and remodeling of new blood vessels from preexisting ones (ie, angiogenesis). Vascular endothelial growth factors (Vegfs) and their endothelial cell-specific receptors play a crucial role in nearly all aspects of blood vessel growth. How the outputs from these pathways affect and coordinate endothelial behavior is an area of intense research. Recently, numerous studies have highlighted roles for microRNAs in modulating Vegf signaling output in several different contexts. In this review, we will provide an overview of how small RNAs regulate multiple aspects of the Vegf signaling pathway. In particular, we highlight areas where identification of microRNAs and their targets has provided new insight into the role of downstream effectors in modulating Vegf output during development. As Vegf plays a broad role in multiple aspects of endothelial biology and has become a target for therapeutic manipulation of pathological blood vessel growth, microRNAs that affect Vegf signaling output will undoubtedly be major targets of clinical value. (Arterioscler Thromb Vasc Biol. 2013;33:193-200)