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Endothelial glycocalyx restoration by growth factors in diabetic nephropathy

Research output: Contribution to journalReview article

Original languageEnglish
Number of pages17
JournalBiorheology
Early online date21 May 2019
DOIs
DateAccepted/In press - 9 May 2019
DateE-pub ahead of print (current) - 21 May 2019

Abstract

The endothelial glycocalyx (eGlx) constitutes the first barrier to protein in all blood vessels. This is particularly noteworthy in the renal glomerulus, an ultrafiltration barrier. Leakage of protein, such as albumin, across glomerular capillaries results in albumin in the urine (albuminuria). This is a hall mark of kidney disease and can reflect loss of blood vessel integrity in microvascular beds elsewhere. We discuss evidence demonstrating that targeted damage to the glomerular eGlx results in increased glomerular albumin permeability. EGlx is lost in diabetes and experimental models demonstrate loss from glomerular endothelial cells. Vascular endothelial growth factor (VEGF)A is upregulated in early diabetes, which is associated with albuminuria. Treatment with paracrine growth factors such as VEGFC, VEGF165b and angiopoietin-1 can modify VEGFA signalling, rescue albumin permeability and restore glomerular eGlx in models of diabetes. Manipulation of VEGF receptor 2 signalling, or a common eGlx biosynthesis pathway by these growth factors, may protect and restore the eGlx layer. This would help to direct future therapeutics in diabetic nephropathy.

    Structured keywords

  • ConDuCT-II

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  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via IOS Press at https://content.iospress.com/articles/biorheology/bir180199 . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 712 KB, PDF document

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