Endothelial glycocalyx restoration by growth factors in diabetic nephropathy

Issue title: Thematic issue on Glycocalyx

Guest editors: John Tarbell and Hans Vink

Article type: Research Article

Authors: Desideri, Sara^{a; †} | Onions, Karen L.^{a; †} | Baker, Siân L.^a | Gamez, Monica^a | El Hegni E Hussien, Hesham^a | Russell, Amy^a | Satchell, Simon C.^a | Foster, Rebecca R.^a;

Affiliations: [a] Bristol Renal, Bristol Heart Institute, Translational Health Sciences, Bristol Medical School, University of Bristol, UK

Correspondence: [*] Corresponding author. E-mail: [email protected]

Note: [†] These authors contributed equally to this work.

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.

Keywords: Endothelial glycocalyx, diabetes, diabetic nephropathy, VEGF, VEGFC, VEGFA, VEGF₁₆₅b, angiopoietin-1, vascular permeability, glomerulus, glomerular permeability

DOI: 10.3233/BIR-180199

Journal: Biorheology, vol. 56, no. 2-3, pp. 163-179, 2019