Department of Anaesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Anaesthesiology, Dongyang Hospital Affiliated to Wenzhou Medical University, Jinhua, China.
J Vasc Res. 2024;61(2):77-88. doi: 10.1159/000537772. Epub 2024 Mar 19.
Previous studies have confirmed that low shear stress (LSS) induces glycocalyx disruption, leading to endothelial dysfunction. However, the role of autophagy in LSS-induced glycocalyx disruption and relevant mechanism are not clear. In this study, we hypothesized that LSS may promote autophagy, disrupting the endothelium glycocalyx.
Human umbilical vein endothelial cells were subjected to physiological shear stress and LSS treatments, followed by the application of autophagy inducers and inhibitors. Additionally, cells were treated with specific matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) inhibitor. The expression of autophagic markers, glycocalyx, MMP-2, and MMP-9 was measured.
LSS impacted the expression of endothelium autophagy markers, increasing the expression of LC3II.LC3I-1 and Beclin-1, and decreasing the levels of p62, accompanied by glycocalyx disturbance. Moreover, LSS upregulated the expression of MMP-2 and MMP-9 and downregulated the levels of syndecan-1 and heparan sulfate (HS). Additionally, expression of MMP-2 and MMP-9 was increased by an autophagy promoter but was decreased by autophagy inhibitor treatment under LSS. Autophagy and MMP-2 and MMP-9 further caused glycocalyx disruption.
LSS promotes autophagy, leading to glycocalyx disruption. Autophagy increases the expression of MMP-2 and MMP-9, which are correlated with the glycocalyx destruction induced by LSS.
先前的研究已经证实，低切应力（LSS）会导致糖萼破坏，从而导致内皮功能障碍。然而，自噬在 LSS 诱导的糖萼破坏中的作用及其相关机制尚不清楚。在这项研究中，我们假设 LSS 可能通过促进自噬来破坏内皮糖萼。
将人脐静脉内皮细胞进行生理切应力和 LSS 处理，然后应用自噬诱导剂和抑制剂。此外，还对特定的基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9）抑制剂进行了处理。测量自噬标志物、糖萼、MMP-2 和 MMP-9 的表达。
LSS 影响内皮细胞自噬标志物的表达，增加 LC3II/LCI-1 和 Beclin-1 的表达，降低 p62 的水平，同时伴有糖萼紊乱。此外，LSS 上调了 MMP-2 和 MMP-9 的表达，降低了 syndecan-1 和硫酸乙酰肝素（HS）的水平。此外，在 LSS 下，自噬促进剂增加了 MMP-2 和 MMP-9 的表达，而自噬抑制剂的处理则降低了它们的表达。自噬和 MMP-2 和 MMP-9 进一步导致糖萼破坏。
LSS 促进自噬，导致糖萼破坏。自噬增加了 MMP-2 和 MMP-9 的表达，这与 LSS 诱导的糖萼破坏有关。
