Getting Tie(2)d up in angiogenesis

Abstract

Angiogenesis, the growth of new vessels from pre-existing blood vessels, requires complex signaling pathways and a high degree of spatial and temporal coordination among various cell types, multiple pro- and anti-angiogenic factors, and their corresponding receptors. Although the targeted disruption of many of these factors leads to embryonic lethal defects in vascular development, the precise actions of these factors at the cellular and molecular levels are not completely defined. Such is the case for angiopoietin-1 (Ang1), angiopoietin-2 (Ang2) and the Ang receptor Tie2. Mice deficient in Ang1, Ang2, or Tie2 exhibit aberrant vascular development, characterized by abnormal interactions between endothelial cells (ECs) and their supporting cells. The abluminal cells of the vasculature, which includes pericytes in the microvasculature and smooth muscle cells (SMCs) in large vessels, are collectively referred to as mural cells (reviewed in ref. 1). In this issue of the JCI, Uemura and colleagues provide some insight into the mechanisms that underlie these defects (2). The authors demonstrate that whereas blocking the function of the PDGF β receptor (PDGFR-β) in the developing retinal vasculature led to mural cell-deficient vessels that were poorly remodeled and leaky, administration of recombinant modified angiopoietin-1 (Ang1*) restored the vascular structure of the larger vessels in the absence of the mural cells.