LRP in Endothelial Cells

Abstract

Endothelial cells are highly heterogeneous1 and participate in angiogenesis, an integrated set of responses in which new blood vessels are formed from existing ones. During angiogenesis, endothelial cells exhibit increased migration and proliferation2 and contribute to the reorganization of the extracellular matrix. Angiogenesis occurs during embryonic development and is also initiated during wound healing and pathological conditions, such as ischemia. Although most often the revascularization of ischemic tissues is highly beneficial, under certain conditions, it can be harmful. For example, pathological angiogenesis in the retina during diabetic retinopathy can result in blindness.3 Several molecules influence angiogenesis, including vascular endothelial growth factor,4 Notch,5 and Wnt.6 In this edition of Atherosclerosis, Thrombosis, and Vascular Biology , Mao et al7 identify another key player in this process: the low-density lipoprotein receptor–related protein 1 (LRP1) by demonstrating a significant role for LRP1 in orchestrating angiogenesis during retinal neovascularization. See accompanying article on page 350 LRP1, is a highly efficient endocytic as well as a signal transducing receptor that binds multiple ligands,8–11 and modulates signaling pathways by regulating the extracellular levels of growth factors and binding adaptor molecules to its intracellular domain (ICD). LRP1 plays an important role in the development12,13 and maintenance of the vasculature.14,15 Deletion of the Lrp1 gene in mice results in early embryonic lethality12 because of extensive hemorrhaging occurring around E13.5.13 The underlying vascular defect results from a failure to recruit and maintain vascular smooth muscle cells and pericytes of vessels resulting in extreme dilation of the aorta with a thin and disorganized smooth muscle cell layer and discontinuity of the vascular endothelium. Interestingly, the phenotype observed for Lrp1 −/− embryos resembles that of mice genetically deficient in sphingosine-1-phosphate receptor S1PR1. Like the …