On the relationship of LDL and VEGFR1: not just a family affair

In this issue of EMBO reports , Usui et al (2007) report their findings of ligand‐independent activation of vascular endothelial growth factor (VEGF) receptor 1 (VEGFR1) by low‐density lipoprotein (LDL). Thus far, VEGFR1 has been shown to be activated only by members of the VEGF ligand family, including VEGF‐A, VEGF‐B and placenta growth factor (PlGF). The new finding indicates indirect activation by a ligand that lies outside this family and suggests a connection between lipoprotein metabolism and vascular signalling through the VEGFR1 pathway. The findings are unexpected, but they could shed light on some previously unexplained findings regarding LDL‐receptor‐mediated signalling and modes of VEGFR1 activation. It is not surprising that researchers in such different fields as lipoprotein metabolism and angiogenesis have not considered the possibility that VEGFRs and LDL receptors might have something in common. Several questions have remained unanswered for decades: How do proliferating …