Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400044, China.
Ann Biomed Eng. 2018 Jun;46(6):849-863. doi: 10.1007/s10439-018-2000-3. Epub 2018 Mar 5.
Inhibitor of DNA binding 1 (Id1) has been shown to be involved in adipogenesis and metabolism, which may contribute to atherosclerotic progression. However, it remains unclear how Id1 regulates endothelial cell functions and atherosclerosis in response to oscillatory shear stress. The current study aims to evaluate the effects of oscillatory shear stress on LDL uptake by endothelial cells and to delineate the roles of Id1 in this process. Using an in vivo ligation model of ApoE mice and applying low and oscillatory shear stress (OSS) in vitro, we found that OSS can effectively promote lipid uptake. In vivo en face staining results showed that OSS down-regulated Id1 expression. In vitro, OSS activated Id1 transiently but eventually inhibited its expression with time. Overexpression of Id1 can abolish OSS-mediated lipid uptake in ECs. In addition, Id1 overexpression and knockdown experiments demonstrated that Id1 can regulate LDLR expression to influence lipid uptake. Immunoprecipitation and subcellular localization results further suggested that Id1 can combine with sterol regulatory element-binding protein1 (SREBP1), which may be related to the Id1-mediated LDLR down-expression. Our study shows a biomechanical role of Id1 in endothelial cells' uptake of lipid by down-regulating LDLR, which could help understand how oscillatory flow affects atherosclerotic development.
DNA 结合抑制因子 1（Id1）已被证明参与脂肪生成和代谢，这可能有助于动脉粥样硬化的进展。然而，Id1 如何调节内皮细胞功能和对振荡剪切应力的动脉粥样硬化仍然不清楚。本研究旨在评估振荡剪切应力对内皮细胞 LDL 摄取的影响，并阐明 Id1 在这一过程中的作用。我们使用载脂蛋白 E （ApoE）小鼠的体内结扎模型，并在体外施加低和振荡剪切应力（OSS），发现 OSS 可以有效地促进脂质摄取。体内正面染色结果表明 OSS 下调了 Id1 的表达。在体外，OSS 短暂激活 Id1，但随着时间的推移最终抑制其表达。Id1 的过表达可以消除 OSS 介导的 ECs 中的脂质摄取。此外，Id1 的过表达和敲低实验表明，Id1 可以调节 LDLR 的表达来影响脂质摄取。免疫沉淀和亚细胞定位结果进一步表明，Id1 可以与固醇调节元件结合蛋白 1（SREBP1）结合，这可能与 Id1 介导的 LDLR 下调有关。我们的研究表明，Id1 通过下调 LDLR 在内皮细胞摄取脂质中具有生物力学作用，这有助于了解振荡流如何影响动脉粥样硬化的发展。
