ArticleAmerican journal of physiology. Renal physiology2011
High glucose causes dysfunction of the human glomerular endothelial glycocalyx.
Article in American journal of physiology. Renal physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 142 citations in OpenAlex.
- Mineralocorticoid receptor antagonism in diabetes reduces albuminuria by preserving the glomerular endothelial glycocalyx.JCI insight · 2023Trial
- Podocyte detachment and reduced glomerular capillary endothelial fenestration promote kidney disease in type 2 diabetic nephropathy.Kidney international · 2012Trial
- Podocyte-derived endothelin-1 and endothelial cell endothelin A receptors are essential for glomerular injury in mouse models of focal segmental glomerulosclerosis.Kidney international · 2026Article
- Mitochondrial Dynamics in Diabetic Kidney Disease: Underlying Mechanisms and Novel Therapeutics.International journal of molecular sciences · 2026Review
- Podocyte-Derived Extracellular Vesicles Induce Endothelial Dysfunction by Triggering ER Stress in Glomerular Disease.Journal of extracellular vesicles · 2026Article
- Vascular and Myocardial Function in Patients with Type 2 Diabetes and Ischemic Stroke Treated with Dulaglutide or Empagliflozin.Medicina (Kaunas, Lithuania) · 2026Observational
- The Association of Diabetes and Atherosclerosis: Understanding the Molecular Mechanism of the Double Burden.Current medicinal chemistry · 2026Review
- Mitochondrial dysfunction: the hidden catalyst in chronic kidney disease progression.Renal failure · 2025Review
- Specificity of endothelial cells in endothelial dysfunction of diabetic kidney disease and their crosstalk with neighboring cells: an updated review.Frontiers in endocrinology · 2025Review
- Vascular Endothelium in Health and Disease: Structure, Function, Assessment and Role in Metabolic Disorders.Vascular health and risk management · 2025Review
- Esm-1 mediates transcriptional polarization associated with diabetic kidney disease.American journal of physiology. Renal physiology · 2024Article
- Leukocyte-endothelial interaction in CKD.Clinical kidney journal · 2023Review
- Insight into the Molecular Mechanism of Diabetic Kidney Disease and the Role of Metformin in Its Pathogenesis.International journal of molecular sciences · 2023Review
- Early diabetic kidney disease: Focus on the glycocalyx.World journal of diabetes · 2023Review
- Endothelial glycocalyx in retina, hyperglycemia, and diabetic retinopathy.American journal of physiology. Cell physiology · 2023Review
- Effects of different dehydration methods on the preservation of aortic and renal glycocalyx structures in mice.Heliyon · 2023Article
- Physiological and pathological characteristics of vascular endothelial injury in diabetes and the regulatory mechanism of autophagy.Frontiers in endocrinology · 2023Review
- Pharmacological functions of salidroside in renal diseases: facts and perspectives.Frontiers in pharmacology · 2023Review
- Effect of high glucose on glycosaminoglycans in cultured retinal endothelial cells and rat retina.Glycobiology · 2022Article
- Endothelial glycocalyx is damaged in diabetic cardiomyopathy: angiopoietin 1 restores glycocalyx and improves diastolic function in mice.Diabetologia · 2022Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
The endothelial glycocalyx is a gel-like layer which covers the luminal side of blood vessels. The glomerular endothelial cell (GEnC) glycocalyx is composed of proteoglycan core proteins, glycosaminoglycan (GAG) chains, and sialoglycoproteins and has been shown to contribute to the selective sieving action of the glomerular capillary wall. Damage to the systemic endothelial glycocalyx has recently been associated with the onset of albuminuria in diabetics. In this study, we analyze the effects of high glucose on the biochemical structure of the GEnC glycocalyx and quantify functional changes in its protein-restrictive action. We used conditionally immortalized human GEnC. Proteoglycans were analyzed by Western blotting and indirect immunofluorescence. Biosynthesis of GAG was analyzed by radiolabeling and quantified by anion exchange chromatography. FITC-albumin was used to analyze macromolecular passage across GEnC monolayers using an established in vitro model. We observed a marked reduction in the biosynthesis of GAG by the GEnC under high-glucose conditions. Further analysis confirmed specific reduction in heparan sulfate GAG. Expression of proteoglycan core proteins remained unchanged. There was also a significant increase in the passage of albumin across GEnC monolayers under high-glucose conditions without affecting interendothelial junctions. These results reproduce changes in GEnC barrier properties caused by enzymatic removal of heparan sulfate from the GEnC glycocalyx. They provide direct evidence of high glucose-induced alterations in the GEnC glycocalyx and demonstrate changes to its function as a protein-restrictive layer, thus implicating glycocalyx damage in the pathogenesis of proteinuria in diabetes.
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