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Angiopoietins and diabetic nephropathy.

Gnudi L - Diabetologia (2016)

Bottom Line: Many vascular growth factors, such as angiopoietins, are implicated in glomerular biology.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.

View Article: PubMed Central - PubMed

Affiliation: Unit for Metabolic Medicine, Cardiovascular Division, Faculty of Life Science & Medicine, King's College London, 3rd Floor Franklin-Wilkins Building, Waterloo Campus, Stamford Street, London, SE1 9RT, UK. luigi.gnudi@kcl.ac.uk.

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.

No MeSH data available.


Related in: MedlinePlus

ANGPT2/ANGPT1 imbalance is paralleled by capillary destabilisation. ANGPT1 is downregulated in early diabetic kidney disease, leading to diabetes-mediated angiopoietin imbalance (ANGPT2 > ANGPT1); ANGPT2 excess results in proteinuria. Repletion of ANGPT1 restores angiopoietin balance (ANGPT1 > ANGPT2) and, acting as a ‘brake’ on vascular lesions, prevents albuminuria and glomerular structural lesions in the early phases of diabetic glomerular disease. Red arrows indicate changes favouring progression towards vascular disease, green arrows point towards changes stimulating a healthy vessel
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Fig1: ANGPT2/ANGPT1 imbalance is paralleled by capillary destabilisation. ANGPT1 is downregulated in early diabetic kidney disease, leading to diabetes-mediated angiopoietin imbalance (ANGPT2 > ANGPT1); ANGPT2 excess results in proteinuria. Repletion of ANGPT1 restores angiopoietin balance (ANGPT1 > ANGPT2) and, acting as a ‘brake’ on vascular lesions, prevents albuminuria and glomerular structural lesions in the early phases of diabetic glomerular disease. Red arrows indicate changes favouring progression towards vascular disease, green arrows point towards changes stimulating a healthy vessel

Mentions: Parallel work from our group has shown that, in the very early stages of diabetic glomerulopathy (3 weeks’ diabetes duration), glomerular Angpt1 mRNA decreases in diabetic mice, with no significant changes in Angpt2 mRNA levels, when compared with non-diabetic animals [24]. This apparent acute effect of elevated circulating glucose levels was also observed in vitro when Angpt1 mRNA was significantly downregulated in high-glucose-treated podocytes compared with normal-glucose-treated cells [24]. Overall, these observations are consistent with the contention that an increased ratio of ANGPT2/ANGPT1 could play a role in the development and progression of glomerular disease in diabetes (Fig. 1).Fig. 1


Angiopoietins and diabetic nephropathy.

Gnudi L - Diabetologia (2016)

ANGPT2/ANGPT1 imbalance is paralleled by capillary destabilisation. ANGPT1 is downregulated in early diabetic kidney disease, leading to diabetes-mediated angiopoietin imbalance (ANGPT2 > ANGPT1); ANGPT2 excess results in proteinuria. Repletion of ANGPT1 restores angiopoietin balance (ANGPT1 > ANGPT2) and, acting as a ‘brake’ on vascular lesions, prevents albuminuria and glomerular structural lesions in the early phases of diabetic glomerular disease. Red arrows indicate changes favouring progression towards vascular disease, green arrows point towards changes stimulating a healthy vessel
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4930459&req=5

Fig1: ANGPT2/ANGPT1 imbalance is paralleled by capillary destabilisation. ANGPT1 is downregulated in early diabetic kidney disease, leading to diabetes-mediated angiopoietin imbalance (ANGPT2 > ANGPT1); ANGPT2 excess results in proteinuria. Repletion of ANGPT1 restores angiopoietin balance (ANGPT1 > ANGPT2) and, acting as a ‘brake’ on vascular lesions, prevents albuminuria and glomerular structural lesions in the early phases of diabetic glomerular disease. Red arrows indicate changes favouring progression towards vascular disease, green arrows point towards changes stimulating a healthy vessel
Mentions: Parallel work from our group has shown that, in the very early stages of diabetic glomerulopathy (3 weeks’ diabetes duration), glomerular Angpt1 mRNA decreases in diabetic mice, with no significant changes in Angpt2 mRNA levels, when compared with non-diabetic animals [24]. This apparent acute effect of elevated circulating glucose levels was also observed in vitro when Angpt1 mRNA was significantly downregulated in high-glucose-treated podocytes compared with normal-glucose-treated cells [24]. Overall, these observations are consistent with the contention that an increased ratio of ANGPT2/ANGPT1 could play a role in the development and progression of glomerular disease in diabetes (Fig. 1).Fig. 1

Bottom Line: Many vascular growth factors, such as angiopoietins, are implicated in glomerular biology.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.

View Article: PubMed Central - PubMed

Affiliation: Unit for Metabolic Medicine, Cardiovascular Division, Faculty of Life Science & Medicine, King's College London, 3rd Floor Franklin-Wilkins Building, Waterloo Campus, Stamford Street, London, SE1 9RT, UK. luigi.gnudi@kcl.ac.uk.

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.

No MeSH data available.


Related in: MedlinePlus