Li Zhuoxin, Sabouri Mostafa, Zheng Xiangyu, Machin Daniel R
Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, United States.
Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, Florida, United States.
Am J Physiol Heart Circ Physiol. 2025 Sep 1;329(3):H765-H773. doi: 10.1152/ajpheart.00491.2025. Epub 2025 Aug 18.
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.
内皮糖萼是内皮上的一种凝胶状结构，在脉管系统中起关键作用。我们已经表明，12周的西式饮食（WD）会增加糖萼厚度和完整性。然而，这些适应性变化的时间进程和促成因素尚不清楚。在WD喂养1、2、4和12周后，我们观察到与年龄匹配的对照饮食喂养小鼠相比，WD小鼠在所有时间点的糖萼厚度和完整性都更大。透明质酸是糖萼的主要成分，有助于其结构和功能完整性。急性给予透明质酸酶可消除WD喂养1周后小鼠糖萼厚度的增加，而对对照饮食喂养小鼠的糖萼厚度没有影响。给予透明质酸酶可增加灌注边界区域（PBR），这是一种糖萼完整性标志物，在WD和对照饮食喂养小鼠中均有增加，但在WD小鼠中增加更为明显，消除了PBR的组间差异。最后，WD减弱了颈动脉中乙酰胆碱介导的血管舒张，表明存在内皮功能障碍。有趣的是，在低流速下，WD喂养小鼠的血流介导的血管舒张得以保留，但在最高流速下，血管舒张减弱。WD小鼠中更大的糖萼厚度可能在给定流速下机械转导更多的剪切应力，在较低流速下保留血流介导的血管舒张，但随着流速增加过早地减弱血管舒张。在WD和对照饮食喂养小鼠中，腔内存在透明质酸酶时，血流介导的血管舒张同样减弱。综上所述，这些发现表明，WD诱导的糖萼特性升高在1周后出现，并且似乎依赖于糖萼中的透明质酸含量。我们观察到，小鼠开始西式饮食后最早在1周就出现了更大的糖萼厚度和完整性。更大的糖萼厚度依赖于糖萼中的透明质酸含量。透明质酸酶消除了对照和WD喂养小鼠之间糖萼完整性的差异。在分离的动脉中，WD喂养小鼠的激动剂介导的血管舒张受损，而血流介导的血管舒张部分得以保留，这表明更厚的糖萼可能补偿了WD喂养小鼠的内皮功能障碍。
