Angiopoietins: Microvascular modulators with potential roles in glomerular pathophysiology

Abstract

Angiopoietins are a recently discovered family of growth factors which act on endothelial cells via Tie receptors. They are widely expressed and have essential roles in regulating vascular growth, development, maturation and permeability. Disturbances in microvascular regulation play an important part in a number of diseases prominent in the developed world including diabetes, ischemic heart disease and cancer. It is the interplay between angiopoietins and other factors including vascular endothelial growth factor (VEGF) which determines endothelial behavior both in health and in these diseases. Angiopoietin-1 is unique in its ability to reduce endothelial permeability and it antagonises the effects of VEGF in its permeability and angiogenesis-inducing actions. The renal glomerulus constitutes a highly specialized microcirculation in which the permeability characteristics of the capillary wall allow its unique filtration function. Disturbance of this function may cause a reduction hi glomerular filtration rate or proteinuria. Understanding of the regulation of the filtration barrier is incomplete but the expression of angiopoietins in the glomerulus suggests a mechanism for maintenance of the glomerular endothelium and modulation of the actions of glomerular VEGF. As has been clearly shown for VEGF, angiopoietins are likely to be involved in glomerular disease and recovery from it. Manipulation of angiopoietins has a wide range of potential therapeutic applications from inhibition of diabetic retinal neovascularisation to promotion of glomerular repair.