LRP-1信号传导调节血管生成的研究进展

Research advances in the role of low-density lipoprotein receptor-related protein-1 signal transduction in regulating in angiogenesis

低密度脂蛋白受体相关蛋白-1(Low-density lipoprotein receptor-related protein-1,LRP-1)在脂质平衡调节、信号传导和胞吞作用中扮演着多重角色,它是许多配体的胞吞作用受体,并且与许多生长因子和细胞因子的信号通路有关。LRP-1的信号传导过程的失调将会导致疾病的形成与发展,如阿尔茨海默氏症、动脉粥样硬化、炎症和凝血等。现在已经出现了关于LRP-1与内皮功能和血管生成的联系的研究,例如在斑马鱼胚胎发育过程研究中,LRP-1是血管网络形成(特别是静脉发育)的必要因素;而小鼠胚胎中的LRP-1敲除可导致血管生成缺陷及内皮完整性的破坏;在氧诱导视网膜病变模型小鼠中,内皮细胞中LRP-1的敲除可导致其新血管的异常发育。综合上述研究表明LRP-1在血管生成过程中起着关键作用。本文综述了血管生成过程中LRP-1信号传导的调节作用及其最新研究进展。

Low-density lipoprotein receptor-related protein-1(LRP-1) is an endocytic receptor for a variety ofligands and plays an important role in lipid balance regulation, signal transduction, and endocytosis. It is involved inthe signaling pathways of various growth factors and cytokines. Dysregulation of LRP-1 signal transduction can leadto the development and progression of diseases such as Alzheimer’s disease, atherosclerosis, inflammation, and coag-ulation disorder. Recent studies have investigated the association of LRP-1 with endothelial function and angiogene-sis. During zebrafish embryonic development, LRP-1 is a necessary factor for the formation of the vascular network,especially venous development, and LRP-1 knockout in mouse embryo can cause defect in angiogenesis and damageof endothelial integrity. In a mouse model of oxygen-induced retinopathy, LRP-1 knockout in endothelial cells maylead to abnormal angiogenesis. The above studies reveal that LRP-1 plays a key role in angiogenesis. The article re-views the regulatory role of LRP-1 signal transduction during angiogenesis and related research advances.