Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
Am J Physiol Heart Circ Physiol. 2021 Apr 1;320(4):H1724-H1737. doi: 10.1152/ajpheart.00861.2020. Epub 2021 Mar 12.
The surface of vascular endothelial cells (ECs) is covered by a protective negatively charged layer known as the endothelial glycocalyx. Herein, we hypothesized its transport barrier and mechanosensory role in transmural water flux and low-density lipoprotein (LDL) transport in an isolated rat abdominal aorta perfused under 85 mmHg and 20 dyn/cm ex vivo. The endothelial glycocalyx was digested by hyaluronidase (HAase) from bovine tests. Water infiltration velocity () was measured by a graduated pipette. LDL coverage and mean maximum infiltration distance (MMID) in the vessel wall were quantified by confocal laser scanning microscopy. EC apoptosis was determined by the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) technique, and leaky junction rates were evaluated by electron microscopy. The results showed that a 42% degradation of the endothelial glycocalyx by HAase treatment increased , LDL coverage, and MMID. Shear stress increased , which cannot be inhibited by HAase treatment. Four hour-shear application increased about fourfolds of LDL coverage, whereas exerted no significant effects on its MMID, EC apoptosis, and the leaky junctions. On the contrary, 24-h shear exposure has no significant effects on LDL coverage, whereas increased 2.74-folds of MMID and about 53% of EC apoptotic rates that could be inhibited by HAase treatment. These results suggest endothelial glycocalyx acts as a transport barrier by decreasing water and LDL transport, as well as a mechanosensor of shear to regulate EC apoptosis, thus affecting leaky junctions and regulating LDL transport into the vessel wall. A 42% degradation of the endothelial glycocalyx by hyaluronidase of the isolated rat abdominal aorta facilitated water and LDL transport across the vessel wall, suggesting endothelial glycocalyx as a transport barrier. A 24-h shear exposure increased LDL mean maximum infiltration distance, and enhanced EC apoptosis, which could be both inhibited by hyaluronidase treatment, suggesting endothelial glycocalyx may also act as a mechanosensor of shear to regulate EC apoptosis, thus affecting leaky junctions and regulating LDL transport.
血管内皮细胞（ECs）的表面覆盖着一层具有保护作用的带负电荷的层，称为内皮糖萼。在这里，我们假设它在跨壁水通量和低密度脂蛋白（LDL）转运中的转运屏障和机械敏感作用，在离体大鼠腹主动脉中，在 85mmHg 和 20dyn/cm 的条件下进行体外灌注。用牛睾丸透明质酸酶（HAase）消化内皮糖萼。通过刻度吸管测量水渗透速度（）。通过共聚焦激光扫描显微镜定量测量血管壁中 LDL 的覆盖范围和平均最大渗透距离（MMID）。通过末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）技术测定 EC 凋亡，用电镜评估渗漏连接率。结果表明，HAase 处理使内皮糖萼降解 42%，增加了，LDL 覆盖范围和 MMID。切应力增加，但不能被 HAase 处理抑制。4 小时切应力应用增加了大约四倍的 LDL 覆盖范围，而对其 MMID、EC 凋亡和渗漏连接没有显著影响。相反，24 小时切应力暴露对 LDL 覆盖范围没有显著影响，而增加了 2.74 倍的 MMID 和大约 53%的 EC 凋亡率，这可以被 HAase 处理抑制。这些结果表明，内皮糖萼作为一种转运屏障，通过降低水和 LDL 的转运，以及作为切应力的机械感受器来调节 EC 凋亡，从而影响渗漏连接并调节 LDL 向血管壁的转运。离体大鼠腹主动脉的透明质酸酶使内皮糖萼降解 42%，促进了水和 LDL 穿过血管壁的转运，表明内皮糖萼是一种转运屏障。24 小时切应力暴露增加了 LDL 的平均最大渗透距离，并增强了 EC 凋亡，这两者都可以被透明质酸酶处理抑制，表明内皮糖萼也可能作为切应力的机械感受器来调节 EC 凋亡，从而影响渗漏连接并调节 LDL 向血管壁的转运。
