细胞外囊泡在主动脉瘤中的研究进展

Research progress on extracellular vesicles in aortic aneurysms

摘要:

主动脉瘤包括胸主动脉瘤(thoracic aortic aneurysm, TAA)和腹主动脉瘤(abdominal aortic aneurysm, AAA)，是一类发病隐匿且致死率高的严重血管病变，目前临床上尚缺乏有效的诊断标志物及药物干预手段。细胞外囊泡(extracellular vesicles, EVs)是细胞间通讯的关键介质，因其携带丰富的生物活性分子且具备良好的生物相容性、低免疫原性和天然靶向性，在主动脉瘤相关研究中日益受到关注。本文系统阐述了EVs在TAA和AAA中的研究进展，重点总结了EVs在主动脉瘤发生发展中的重要作用。EVs通过介导内皮功能障碍、血管平滑肌细胞表型转换、炎症免疫反应及细胞外基质重塑等核心病理过程发挥重要作用。同时，本文探讨了EVs携带的疾病特异性分子在主动脉瘤早期诊断中展现出作为新型液体活检标志物的潜力。此外，还评估了EVs作为天然药物递送平台及基于工程化修饰(如靶向肽修饰、生物材料结合)的主动脉瘤治疗策略的应用前景，尤其是通过工程化修饰增强其对病变部位的靶向能力，以调控关键免疫细胞(如巨噬细胞)表型与功能为策略核心的“无细胞”免疫调节疗法，日益成为该领域最具转化潜力的前沿方向。尽管面临靶向递送等挑战，但随着工程化技术与纳米医学的融合，基于EVs的诊疗一体化策略有望为主动脉瘤的精准防治开辟新路径。

Abstract:

Aortic aneurysms, including thoracic aortic aneurysms (TAA) and abdominal aortic aneurysms (AAA), represent a group of severe vascular lesions with insidious onset and high mortality. Currently, effective diagnostic markers and pharmacological interventions remain lacking in clinical practice. Extracellular vesicles (EVs), as key mediators of intercellular communication, have attracted increasing attention in the research on aortic aneurysms due to their high content of bioactive molecules, favorable biocompatibility, low immunogenicity, and inherent targeting capacity. This review systematically elaborated on the research progress on EVs in TAA and AAA, highlighting their significant role in the development and progression of aortic aneurysms. EVs play a crucial role by mediating core pathological processes, including endothelial dysfunction, phenotypic transformation of vascular smooth muscle cells, inflammatory immune responses, and extracellular matrix remodeling. Additionally, this review discussed the potential of disease-specific molecules carried by EVs as novel liquid biopsy markers for the early diagnosis of aortic aneurysms. Furthermore, this review evaluated the application prospects of EVs as natural drug delivery platforms and EV-based therapeutic strategies for aortic aneurysm through engineering modifications (such as targeting peptide modification and biomaterial integration). In particular, “cell-free” immunomodulatory therapies, which enhance targeting capacity to lesion sites through engineering modifications and focus strategically on regulating the phenotype and function of key immune cells (such as macrophages), are increasingly emerging as a cutting-edge direction with the greatest translational potential in this field. Despite challenges such as targeted delivery, the integration of engineering technologies with nanomedicine holds promise for opening new avenues for the precise prevention and treatment of aortic aneurysms through EV-based integrated diagnostic and therapeutic strategies.