Department of Pathogenobiology, The Key Laboratory of Zoonosis, Chinese Ministry of Education, College of Basic Medicine, Jilin University, Changchun, 130021, China.
Department of Immunology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, Xinjiang, 830000, China.
J Cell Sci. 2022 Jul 15;135(14). doi: 10.1242/jcs.259696. Epub 2022 Jul 22.
Laminar shear stress (Lss) is an important anti-atherosclerosis (anti-AS) factor, but its mechanism network is not clear. Therefore, this study aimed to identify how Lss acts against AS formation from a new perspective. In this study, we analyzed high-throughput sequencing data from static and Lss-treated human aortic and human umbilical vein endothelial cells (HAECs and HUVECs, respectively) and found that the expression of CX3CL1, which is a target gene closely related to AS development, was lower in the Lss group. Lss alleviated the inflammatory response in TNF-α (also known as TNF)-activated HAECs by regulating the miR-29b-3p/CX3CL1 axis, and this was achieved by blocking nuclear factor (NF)-κB signaling. In complementary in vivo experiments, a high-fat diet (HFD) induced inflammatory infiltration and plaque formation in the aorta, both of which were significantly reduced after injection of agomir-miRNA-29b-3p via the tail vein into HFD-fed ApoE-/- mice. In conclusion, this study reveals that the Lss-sensitive miR-29b-3p/CX3CL1 axis is an important regulatory target that affects vascular endothelial inflammation and AS development. Our study provides new insights into the prevention and treatment of AS.
层流切应力（Lss）是一种重要的抗动脉粥样硬化（抗 AS）因子，但它的机制网络尚不清楚。因此，本研究旨在从新的角度探讨 Lss 如何对抗 AS 的形成。在这项研究中，我们分析了来自静态和 Lss 处理的人主动脉和人脐静脉内皮细胞（HAECs 和 HUVECs）的高通量测序数据，发现 AS 发展密切相关的靶基因 CX3CL1 在 Lss 组中的表达较低。Lss 通过调节 miR-29b-3p/CX3CL1 轴来减轻 TNF-α（也称为 TNF）激活的 HAECs 的炎症反应，这是通过阻断核因子（NF）-κB 信号通路实现的。在补充的体内实验中，高脂饮食（HFD）诱导主动脉中的炎症浸润和斑块形成，而在通过尾静脉向 HFD 喂养的 ApoE-/- 小鼠中注射 agomir-miRNA-29b-3p 后，这些都明显减少。总之，本研究揭示了 Lss 敏感的 miR-29b-3p/CX3CL1 轴是影响血管内皮炎症和 AS 发展的重要调节靶点。我们的研究为 AS 的预防和治疗提供了新的见解。
