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Glycocalyx degradation impairs endothelial function in cultured cells and a mouse model of type 2 diabetes
Author(s) -
Ghiarone Thaysa,
Foote Christopher A.,
Padilla Jaume,
MartinezLemus Luis A.
Publication year - 2018
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.2018.32.1_supplement.lb275
Subject(s) - glycocalyx , neuraminidase , umbilical vein , vasodilation , endothelium , endocrinology , medicine , chemistry , biology , immunology , in vitro , biochemistry , virus
The endothelial glycocalyx is a critical component of the vascular intima putatively essential for the mechanotransduction of shear stress and arterial flow‐mediated dilation (FMD). Neuraminidase degrades the glycocalyx and is elevated in the plasma of patients with type 2 diabetes (T2D) and a mouse model of insulin resistance. Therefore, we hypothesized that exposure of cultured endothelial cells and isolated arteries to neuraminidase would degrade the glycocalyx and impair FMD, while neuraminidase inhibition in vivo would improve arterial FMD in a mouse model of T2D. Methods Human umbilical vein endothelial cells (HUVECs) in culture were treated with neuraminidase (125 mU) for 1h and subsequently assessed for glycocalyx content by immunocytochemistry. Isolated mouse mesenteric arteries were also treated with neuraminidase and evaluated for FMD. In addition, T2D db/db mice were treated with the neuraminidase inhibitor, Zanamivir (10mg/day) for 5 days and their femoral arteries isolated and tested for FMD and acetylcholine‐induced vasodilation. Results Neuraminidase reduced Syndecan‐1 staining by 43% and presence of glycosaminoglycans by 28% in HUVECs, indicating a significant (P<0.05) reduction in glycocalyx content. Mesenteric arteries exposed to neuraminidase displayed a significant (P<0.05) reduction in FMD. In addition, treatment of db/db mice with Zanamivir significantly improved FMD and acetylcholine‐induced vasodilation in isolated femoral arteries, while reducing serum neuraminidase activity in plasma. Conclusion Our results demonstrate that neuraminidase reduces glycocalyx content in endothelial cells and impairs FMD in isolated arteries. Furthermore, neuraminidase inhibition improved overall endothelial function suggesting that targeting neuraminidase may be a viable treatment for endothelial dysfunction in the setting of T2D. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .