VEGF Signaling

Vivienne C. Ho, Guo-Hua Fong, Ho, Vivienne C., Fong, Guo-Hua

Vascular endothelial growth factor receptor-1 (VEGFR-1)/Flt-1 is a transmembrane tyrosine kinase receptor for VEGF-A, VEGF-B, and placental growth factor (PlGF). VEGFR-1 is an enigmatic molecule whose precise role in postnatal angiogenesis remains controversial. Although many postnatal and adult studies have been performed by manipulating VEGFR-1 ligands, including competitive binding by truncated VEGFR-1 protein, neutralization by antibodies, or specific ligand overexpression or knockout, much less is known at the level of the receptor per se, especially in vivo. Perplexingly, while VEGFR-1 negatively regulates endothelial cell differentiation during development, it has been implied in promoting angiogenesis under certain conditions in adult tissues, especially in tumors and ischemic tissues. Additionally, it is unclear how VEGFR-1 is involved in vascular maturation and maintenance of vascular quiescence in adult tissues. To facilitate further investigation, we generated a conditional knockout mouse line for VEGFR-1 and characterized angiogenesis in postnatal and adult mice, including angiogenesis in ischemic myocardium. These methods are briefly outlined in this chapter. We also discuss these findings in the context of the interplay between VEGF family members and their receptors, and summarize various mouse models in the VEGF pathway.