Hyaluronidase 1 deficiency preserves endothelial function and glycocalyx integrity in early streptozotocin-induced diabetes

Sophie Dogné, Géraldine Rath, François Jouret, Nathalie Caron, Chantal Dessy, Bruno Flamion

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

Hyaluronic acid (HA) is amajor component of the glycocalyx involved in the vascular wall and endothelial glomerular permeability barrier. Endocytosed hyaluronidase HYAL1 is known to degrade HA into small fragments in different cell types, including endothelial cells. In diabetes, the size and permeability of the glycocalyx are altered. In addition, patients with type 1 diabetes present increased plasma levels of both HA and HYAL1. To investigate the potential implication of HYAL1 in the development of diabetes-induced endotheliumdysfunction, wemeasured endothelialmarkers, endothelium-dependent vasodilation, arteriolar glycocalyx size, and glomerular barrier properties in wild-type and HYAL1 knockout (KO) mice with or without streptozotocin (STZ)-induced diabetes. We observed that 4 weeks after STZ injections, the lack of HYAL1 1) prevents diabetes-induced increases in soluble P-selectin concentrations and limits the impact of the disease on endothelium-dependent hyperpolarization (EDH)- mediated vasorelaxation; 2) increases glycocalyx thickness and maintains glycocalyx structure and HA content during diabetes; and 3) prevents diabetes-induced glomerular barrier dysfunction assessed using the urinary albumin-to-creatinine ratio and urinary ratio of 70- to 40-kDa dextran. Our findings suggest that HYAL1 contributes to endothelial and glycocalyx dysfunction induced by diabetes. HYAL1 inhibitors could be explored as a new therapeutic approach to prevent vascular complications in diabetes.

langueAnglais
Pages2742-2753
Nombre de pages12
journalDiabetes
Volume65
Numéro9
Les DOIs
étatPublié - 1 sept. 2016

Empreinte digitale

Glycocalyx
Experimental Diabetes Mellitus
Hyaluronic Acid
Vasodilation
Endothelium
Blood Vessels
Permeability
P-Selectin
Hyaluronoglucosaminidase
Diabetes Complications
Streptozocin
Endocytosis
Dextrans
Type 1 Diabetes Mellitus
Knockout Mice
Hyaluronidase Deficiency
Albumins
Creatinine
Endothelial Cells
Injections

Citer ceci

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Hyaluronidase 1 deficiency preserves endothelial function and glycocalyx integrity in early streptozotocin-induced diabetes. / Dogné, Sophie; Rath, Géraldine; Jouret, François; Caron, Nathalie; Dessy, Chantal; Flamion, Bruno.

Dans: Diabetes, Vol 65, Numéro 9, 01.09.2016, p. 2742-2753.

Résultats de recherche: Contribution à un journal/une revueArticle

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T1 - Hyaluronidase 1 deficiency preserves endothelial function and glycocalyx integrity in early streptozotocin-induced diabetes

AU - Dogné, Sophie

AU - Rath, Géraldine

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AU - Flamion, Bruno

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