Time course and contributors to greater glycocalyx thickness and integrity following Western diet consumption.

The endothelial glycocalyx is a gel-like structure on the endothelium that plays a critical role in vasculature. We have shown that 12 wk of a Western diet (WD) increases glycocalyx thickness and integrity. However, the time course and contributors to these adaptations are unknown. After 1, 2, 4, and 12 wk of WD, we observed greater glycocalyx thickness and integrity at all time points in WD mice compared with age-matched control diet-fed mice. Hyaluronan is a major component of the glycocalyx that contributes to its structural and functional integrity. Acute hyaluronidase administration eliminated elevations in glycocalyx thickness in mice following 1 wk of WD, while having no effect on glycocalyx thickness in control diet-fed mice. Hyaluronidase administration increased perfused boundary region (PBR), a glycocalyx integrity marker, in both WD and control diet-fed mice, but more so in WD mice, eliminating group differences in PBR. Lastly, WD blunted acetylcholine-mediated vasodilation in carotid arteries, indicating endothelial dysfunction. Interestingly, flow-mediated vasodilation was preserved at low flow rates in WD-fed mice, yet at the highest flow rate, vasodilation was blunted. Greater glycocalyx thickness in WD mice may mechanotransduce more shear stress at a given flow rate, preserving flow-mediated vasodilation at lower flow rates, but prematurely blunting vasodilation as flow rate increases. Flow-mediated vasodilation was similarly blunted in the presence of intraluminal hyaluronidase in WD and control diet-fed mice. Taken together, these findings demonstrate that WD-induced elevations in glycocalyx properties occur after 1 wk and appear to be dependent on hyaluronan content in the glycocalyx. We observed greater glycocalyx thickness and integrity starting as early as 1 wk after mice began a Western diet. Greater glycocalyx thickness was dependent on the hyaluronan content in the glycocalyx. Differences in glycocalyx integrity between control and Western diet-fed mice were eliminated by hyaluronidase. In isolated arteries, agonist-mediated vasodilation was impaired in Western diet-fed mice, while flow-mediated vasodilation was partially preserved, suggesting a thicker glycocalyx may compensate for endothelial dysfunction in Western diet-fed mice.