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Hyaluronidase 1 Deficiency Preserves Endothelial Function and Glycocalyx Integrity in Early Streptozotocin-Induced Diabetes
- Source :
- Diabetes. 65(9)
- Publication Year :
- 2015
-
Abstract
- Hyaluronic acid (HA) is a major 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 endothelium dysfunction, we measured endothelial markers, 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.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Endothelium
Endocrinology, Diabetes and Metabolism
Hyaluronoglucosaminidase
Vasodilation
030204 cardiovascular system & hematology
Biology
Glycocalyx
Diabetes Mellitus, Experimental
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Hyaluronidase
Diabetes mellitus
Internal medicine
Hyaluronic acid
Internal Medicine
medicine
Animals
RNA, Messenger
Hyaluronic Acid
Mice, Knockout
Type 1 diabetes
medicine.disease
Streptozotocin
Mice, Inbred C57BL
030104 developmental biology
Endocrinology
medicine.anatomical_structure
chemistry
Immunology
Endothelium, Vascular
medicine.drug
Subjects
Details
- ISSN :
- 1939327X
- Volume :
- 65
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....dfd46fdeae04e95a51c0bd5912bcfd05