An imbalance in the angiopoietin system, specifically an increased ANGPT2 to ANGPT1 ratio, drives the cellular mechanisms that mediate diabetic glomerular pathology.
Diabetic nephropathy is the main cause of end-stage renal failure in the Western world. In diabetes, metabolic and haemodynamic perturbations disrupt the integrity of the glomerular filtration barrier, leading to ultrastructural alterations of the glomeruli, including podocyte foot process fusion and detachment, glomerular basement membrane thickening, reduced endothelial cell glycocalyx, and mesangial extracellular matrix accumulation and glomerulosclerosis, ultimately leading to albuminuria and end-stage renal disease. Many vascular growth factors, such as angiopoietins, are implicated in glomerular biology. In normal physiology angiopoietins regulate the function of the glomerular filtration barrier. When they are dysregulated, however, as they are in diabetes, they drive the cellular mechanisms that mediate diabetic glomerular pathology. Modulation of angiopoietins expression and signalling has been proposed as a tool to correct the cellular mechanisms involved in the pathophysiology of diabetic microvascular disease, such as retinopathy in humans. Future work might evaluate whether this novel therapeutic approach should be extended to diabetic kidney disease.
Luigi Gnudi (Fri,) conducted a review in Diabetic nephropathy. Angiopoietin imbalance (increased ANGPT2/ANGPT1 ratio) was evaluated. An imbalance in the angiopoietin system, specifically an increased ANGPT2 to ANGPT1 ratio, drives the cellular mechanisms that mediate diabetic glomerular pathology.