Identifying the time course and contributors for Western diet-induced increase in glycocalyx barrier function

Abstract

The endothelial glycocalyx is a dynamic gel-like structure bound to the vascular endothelium composed of glycosaminoglycans, such as hyaluronan. The glycocalyx plays a critical role in cardiovascular health, acting as a physical barrier to the contents of flowing blood, including red blood cells. Interestingly, we have shown that 12 weeks of Western diet (WD), characterized by excess saturated fat and sugar content, results in greater glycocalyx barrier function in the mesenteric microcirculation that is strongly related to blood glucose values. Currently, the time course that WD induces an increase in glycocalyx barrier function is unknown, as are the contributors to that increase. Thus, we first examined glycocalyx barrier function 1, 2, 4, and 12 weeks after initiating WD in non-fasted male and female UM-HET3 mice (n=9-14/group). Glycocalyx barrier function was assessed in the mesenteric microcirculation by determining perfused boundary region (PBR), which represents red blood cell penetration into the glycocalyx. A higher PBR indicates worse glycocalyx barrier function. Compared to age-matched normal chow (NC) control mice, PBR was lower in WD at week 1 (NC: 2.35±0.05 vs. WD: 1.94±0.04 μm, p<0.05), 2 (NC: 2.36±0.04 vs. WD: 2.01±0.07 μm, p<0.05), 4 (NC: 2.38±0.04 vs. WD: 1.91±0.1 μm, p<0.05), and 12 (NC: 2.41±0.03 vs. WD 1.99±0.04 μm, p<0.05). While blood glucose was higher in WD compared to NC mice at week 12 (NC: 166±3 vs. WD 179±4 mg/dL, p<0.05), it was similar between NC and WD at week 1, 2, and 4 (P>0.05). These data indicate that the WD-induced increase in glycocalyx barrier function occurs as early as 1 week after initiating WD and appears to be independent of blood glucose. Because glycocalyx barrier function was assessed in the mesenteric microcirculation in non-fasted mice, we then sought to determine if the WD-induced increase in glycocalyx barrier function was due to postprandial state. Thus, we determined PBR in non-fasted and fasted (6h) male and female UM-HET3 mice 1 week after initiating WD (n=14-16/group). Fasting status did not affect PBR in age-matched NC (non-fasted 2.32±0.05 vs. fasted: 2.25±0.04 μm, P>0.05) or WD mice (non-fasted 1.94±0.04 vs. fasted: 2.06±0.05 μm, P>0.05), though WD had lower PBR than NC mice in non-fasted and fasted states (p<0.05). These data indicate that glycocalyx barrier function is unaffected by fasting status. Given the role of hyaluronan in the glycocalyx, we then sought to determine if the WD-induced increase in glycocalyx barrier function was due to higher hyaluronan content in the glycocalyx. Thus, we examined PBR pre- and 30 min post-hyaluronidase administration (35 U) in male and female UM-HET3 mice 1 week after initiating WD (n=5/group). There was a tendency for hyaluronidase administration to increase PBR in age-matched NC mice (Pre: 2.37±0.07 vs. Post: 2.65±0.12 μm, P=0.11), whereas PBR increased in WD mice after hyaluronidase administration (Pre: 2.13±0.04 vs. Post: 2.53±0.09 μm, p<0.05). Additionally, the difference in PBR between NC and WD mice was no longer present post-hyaluronidase administration (P>0.05). Taken together, these data indicate that glycocalyx barrier function is increased as early as 1 week after initiating WD and appears to be independent of blood glucose or fasting status but is at least partially due to increased hyaluronan content in the glycocalyx. This study was partly funded by a grant from the National Institutes of Health (R00 AT010017). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.