腹部大動脈瘤治療における新規治療標的：最近の前臨床研究からのエビデンス

The absence of any treatment for small abdominal aortic aneurysm (AAA) highlights the urgent need for an effective drug therapy.

This review examined recent evidence from research involving mouse models of AAA aimed at investigating novel drug targets to limit AAA growth and rupture which validated findings using patient samples. Mechanisms implicated in AAA pathogenesis identified included extracellular matrix remodeling, lipid metabolism dysregulation, inflammatory and immune mediators, microRNA and epigenetic dysregulation and pro-thrombotic pathways.

Future research should focus on developing animal models that more accurately mimic human AAA to reliably test the effect of drug targets. Improving targeting specificity and minimizing systemic exposure by achieving targeted delivery of nanoparticles or adeno-associated viral vectors could be crucial to enhance efficacy and safety. A well-designed systematic integrated cross-species analysis of single-cell RNA-sequencing data from human AAA and different models of animal AAA could be of value to identify differentially expressed genes across species, highlight conserved therapeutic targets, reveal which AAA induction method appropriately models each aspects of the human disease, and guide the selection of animal models, thereby enhancing translational relevance.