Abstract
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.
Highlights
Angiopoietins are vascular growth factors involved in vasculogenesis and vascular repair
Glomerular capillaries are unique in their structure: they are composed of a fenestrated endothelium, which sits on a basement membrane, and specialised epithelial cells, which cover the external layers of the glomerular filter with their interdigitating foot processes
Work by different investigators has highlighted the presence of an autocrine/paracrine network consisting of angiopoietins and other vasoactive peptides regulating the physiology of the glomerular capillaries in Diabetologia (2016) 59:1616–1620 terms of blood flow and permeability of the vascular wall
Summary
Angiopoietins are vascular growth factors involved in vasculogenesis and vascular repair. Work by different investigators has highlighted the presence of an autocrine/paracrine network consisting of angiopoietins and other vasoactive peptides regulating the physiology of the glomerular capillaries in Diabetologia (2016) 59:1616–1620 terms of blood flow and permeability of the vascular wall. An imbalance in these vasoactive peptides promotes endothelial dysfunction: one of the earliest mechanisms of vascular chronic complications in diabetes. Many recent studies have proposed a complex local autocrine/paracrine network consisting of vascular growth factors and vasoactive peptides secreted by glomerular cells which exert their action by binding to their specific receptor on podocytes and glomerular endothelial cells. Tie ( known as Tek) expression is localised in developing and adult mouse glomerular capillaries mainly at the level of the endothelium [20, 23], while some reports show its expression in mouse and rat podocytes in vivo [21, 24]
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