Novel therapeutic targets for abdominal aortic aneurysm treatment: evidence from recent preclinical research.

Abstract

INTRODUCTION: The absence of any treatment for small abdominal aortic aneurysm (AAA) highlights the urgent need for an effective drug therapy. AREAS COVERED: 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. EXPERT OPINION: Future research should focus on developing animal models that more accurately mimic human AAA to reliably test the effect of drug targets. Improving drug 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 aspect of the human disease, and guide the selection of animal models, thereby enhancing translational relevance.