The modification of a factor that promotes angiogenesis - the formation of new blood vessels - specifically in response to injury is reported online this week in Nature Cell Biology. The findings shed light on how the cells of blood vessels respond to injury, and could provide the basis for selective therapeutic intervention against pathological angiogenesis.
Paul Fox and colleagues discover that profilin-1 (Pfn-1), a regulator of the actin component of the cellular skeleton, is modified in response to the growth factor VEGF-A - a key inducer of angiogenesis during development and tissue repair. The authors demonstrated that recognition of VEGF-A by the cellular VEGF receptor 2 (VEGFR2) triggers VEGFR2-mediated addition of a phosphate group to Pfn-1. This modification of Pfn-1 then promotes the reorganizsation of the actin network and the guided migration of endothelial cells that form the vasculature, a certain process that is necessary for angiogenesis. The authors further generated transgenic mice deficient for the VEGFR2-mediated Pfn-1 modification. They, and show that although these mice develop normally, they have defects in endothelial cell migration and angiogenesis following injury, which is similar to that caused by wounding of the skin or by conditions that lead to restricted blood supply to tissues.