Wang Wanting, Chang Siyao, Zhao Gang
Heilongjiang University of Chinese Medicine, Heilongjiang, Harbin, China.
Vascular Surgery Department, Harbin Fifth Hospital, Harbin, China.
Front Immunol. 2025 Aug 27;16:1668203. doi: 10.3389/fimmu.2025.1668203. eCollection 2025.
Thromboangiitis obliterans (TAO) is a non-atherosclerotic, inflammatory vasculopathy characterized by thrombotic occlusion of small- and medium-sized vessels, leading to tissue ischemia and gangrene. Emerging evidence underscores endothelial cell (EC) activation as a central driver of disease progression, mediated by immune dysregulation, oxidative stress (Nrf2/ROS imbalance), impaired nitric oxide signaling (eNOS/iNOS dysregulation), endoplasmic reticulum and mitochondrial dysfunction, and disrupted copper/iron homeostasis. These pathways collectively promote a prothrombotic, proinflammatory endothelial phenotype, perpetuating vascular injury. Current therapies primarily alleviate symptoms but fail to address underlying EC dysfunction. Recent advances, including stem cell therapy and targeted immunomodulation, offer promising avenues for restoring endothelial homeostasis. However, translating mechanistic insights into durable clinical benefits requires further research into precision medicine approaches and large-scale validation of novel therapeutics. This review summarizes the multifactorial pathogenesis of TAO, emphasizing EC activation as a therapeutic linchpin, and outlines future directions to bridge translational gaps in disease management.
血栓闭塞性脉管炎（TAO）是一种非动脉粥样硬化性炎症性血管病，其特征是中小血管的血栓性闭塞，导致组织缺血和坏疽。新出现的证据强调内皮细胞（EC）激活是疾病进展的核心驱动因素，由免疫失调、氧化应激（Nrf2/ROS失衡）、一氧化氮信号受损（eNOS/iNOS失调）、内质网和线粒体功能障碍以及铜/铁稳态破坏介导。这些途径共同促进促血栓、促炎的内皮表型，使血管损伤持续存在。目前的治疗主要缓解症状，但未能解决潜在的内皮细胞功能障碍。包括干细胞治疗和靶向免疫调节在内的最新进展为恢复内皮稳态提供了有希望的途径。然而，将机制性见解转化为持久的临床益处需要进一步研究精准医学方法并对新型疗法进行大规模验证。本综述总结了TAO的多因素发病机制，强调内皮细胞激活作为治疗关键，并概述了弥合疾病管理中转化差距的未来方向。
