Exosome-mediated macrophage regulation in abdominal aortic aneurysm treatment

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease characterized by the irreversible dilatation of the aortic wall. AAA progression is closely linked to an imbalance in macrophage polarization, chronic inflammation, and the degradation of the extracellular matrix (ECM). This review expounded on the potential role of exosomes, as natural bioactive carriers, in modulating macrophage polarization, metabolic reprogramming, and pyroptosis by delivering various biomolecules, including non-coding RNAs (ncRNAs), proteins, and lipids, thereby influencing the pathogenesis of AAA. Exosomes facilitate intercellular communication in AAA by transferring bioactive molecules that potentially influence macrophage polarization and inflammatory responses through various mechanisms. These include the inhibition of NLRP3 inflammasome activation, modulation of the balance between glycolysis and oxidative phosphorylation, as well as targeting key signaling pathways such as PARP-1/PP-1α/JNK/c-Jun and TSC2-mTOR-AKT. Moreover, engineered exosomes, such as those modified with targeting peptides, magnetic nano-drug delivery systems, and hydrogel-based sustained-release platforms, are currently being investigated to improve lesion targeting and therapeutic durability, thereby offering a promising multidimensional intervention strategy for AAA treatment. However, the clinical application of exosomes continues to encounter several challenges, including the absence of standardized production protocols, obstacles in large-scale preparation, and inadequate safety verification. Future research should prioritize a comprehensive analysis of the exosome-macrophage interaction network, the development of advanced delivery systems, and the validation of preclinical efficacy. These efforts are indeed crucial for advancing the translational application of exosome-based immunomodulatory strategies in the treatment of AAA.