Yuan Xiaofan, Shen Guanru, Xiao Hongmei, Wang Zijie, Ma Yue, Qin Xinyue
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Yixueyuan Road, Chongqing, Yuzhong District, China.
Cardiovasc Drugs Ther. 2025 Feb;39(1):211-219. doi: 10.1007/s10557-023-07478-5. Epub 2023 Jul 13.
Neuronal guidance proteins (NGPs) have been demonstrated to guide the elongation of neuronal axonal growth cones in the developing central nervous system. Non-neuronal functions of NGPs have also been described, especially in relation to atherosclerosis.
Netrin-1 and repulsive guidance molecule a (RGMa) are NGPs that have been shown to regulate endothelial cell adhesion and angiogenesis, macrophage migration and apoptosis, smooth muscle cells (SMCs) phenotypic dedifferentiation and mobility, chemokine activities, and inflammatory responses during atherosclerosis initiation and progression.
However, mechanistic studies have generated controversy about the specific role of Netrin-1 in atherosclerosis due to the diversity of its structure, receptors and cell sources, and the actions of RGMa in atherosclerosis have not been reported in previous reviews. Therefore, the current work reviews the evidence for roles of Netrin-1 and RGMa in the initiation and progression of atherosclerosis and discusses potential therapeutic targets in the future.
神经元导向蛋白（NGPs）已被证明在发育中的中枢神经系统中引导神经元轴突生长锥的伸长。NGPs的非神经元功能也有相关描述，尤其是与动脉粥样硬化相关的功能。
Netrin-1和排斥性导向分子a（RGMa）是NGPs，已被证明在动脉粥样硬化的起始和进展过程中调节内皮细胞黏附、血管生成、巨噬细胞迁移和凋亡、平滑肌细胞（SMC）表型去分化和迁移、趋化因子活性以及炎症反应。
然而，由于Netrin-1结构、受体和细胞来源的多样性，其在动脉粥样硬化中具体作用的机制研究存在争议，且之前的综述中尚未报道RGMa在动脉粥样硬化中的作用。因此，本研究综述了Netrin-1和RGMa在动脉粥样硬化起始和进展中作用的证据，并探讨了未来潜在的治疗靶点。
