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Hyal‐1 deficiency may protect the endothelium in a mouse diabetic model (1076.4)
Author(s) -
Dogne Sophie,
Rath Geraldine,
Dessy Chantal,
Caron Nathalie,
Flamion Bruno
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1076.4
Subject(s) - glycocalyx , medicine , endocrinology , streptozotocin , vascular permeability , diabetes mellitus , endothelium , basal (medicine) , hyaluronic acid , endothelial dysfunction , chemistry , immunology , anatomy
Background . Hyaluronic acid (HA) is a major component of the glycocalyx and thereby participates in vascular wall permeability. In diabetes, the size and permeability of the glycocalyx are altered. In addition, type 1 diabetic patients have increased plasma levels of both HA and its somatic hyaluronidase Hyal‐1, which is endocytosed by different cell types including endothelial cells. Objective . To investigate the potential implication of Hyal‐1 in the development of endothelium dysfunction linked to diabetes. Methods . Plasma HA and ICAM‐1/VCAM‐1, myocardial capillary glycocalyx (using transmission electron microscopy) and mesenteric artery endothelial dysfunction were measured in Hyal‐1 KO mice and wild‐type (WT) mice made diabetic by daily injections of streptozotocin during 5 days. Results . KO mice had higher plasma HA concentrations than WT mice. Plasma HA increased with diabetes in the WT mice but did not increase further in KO mice. Basal plasma levels of ICAM‐1 and VCAM‐1 were lower in Hyal‐1 KO than in WT mice. ICAM‐1 but not VCAM‐1 was significantly up‐regulated by diabetes. The glycocalyx had a similar baseline thickness in KO vs WT mice but reacted in opposite ways to 4 weeks of hyperglycemia, almost disappearing in WT mice while increasing in KO mice. Endothelium‐dependent vasodilation did not differ between healthy WT and KO mice. However, in WT diabetic mice, EDHF‐mediated vasorelaxation vanished whereas KO diabetic mice had a preserved EDHF pathway. Conclusion . Decreased levels of Hyal‐1 or increased plasma levels of HA orient the diabetic endothelial response towards a reinforced glycocalyx, less inflammation, and a lesser damage to the EDHF‐dependent vasodilation pathway. The mechanisms of this protection are under current investigation.