Beyond tie-ing up endothelial adhesion: new insights into the action of angiopoietin-1 in regulation of microvessel permeability

The growth factor angiopoietin-1 (Ang1) has been identified as the primary activating ligand for Tie2, a tyrosine kinase receptor highly expressed in vascular endothelial cells.1 Genetic studies using targeted mutations in mice have demonstrated that Tie2 activation by Ang1 is crucial for angiogenesis, vascular remodelling, and vascular maturation.2 However, the angiogenic functions of Ang1 are distinct from those of vascular endothelial growth factor (VEGF). Transgenic mice studies have revealed that blood vessels induced by VEGF overexpression are leaky, whereas blood vessels induced by Ang1 overexpression are not only non-leaky, but also resistant to vascular leakage during inflammation.3 Previous studies using inflammatory mediator-stimulated animals or cultured endothelial cells have identified the permeability protective effects of Ang1 to be mediated through inhibition of endothelial gap formation4 and strengthening of endothelial adhesion.5 In a new study featured in this issue of Cardiovascular Research , Salmon et al. 6 report the effect of Ang1 on the endothelial glycocalyx and propose a novel mechanism for the permeability protective action of Ang1.Using individually perfused mesenteric microvessels with the Landis-Michel technique,7,8 Salmon et al. quantified the direct effect of Ang1 on water and albumin permeability in intact microvessels by measuring permeability … *Corresponding author. Tel: +1 304 293 1515; fax: +1 304 293 3850. E-mail address : phe{at}hsc.wvu.edu