A Novel Role of Id1 in Regulating Oscillatory Shear Stress-Mediated Lipid Uptake in Endothelial Cells

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.