Abdominal aortic aneurysm progression: A review of preclinical and clinical data.

Despite advancements in surgical and endovascular interventions and improved screening protocols, abdominal aortic aneurysm (AAA) remains a progressive vascular condition associated with significant morbidity and mortality owing to rupture. However, the mechanisms underlying the progression of AAA are poorly understood. AAA progression is driven by complex biological mechanisms, including endothelial dysfunction, chronic inflammation, extracellular matrix (ECM) degradation, proteolytic activity, and vessel wall remodeling. Some studies highlight proteases like matrix metalloproteinases in ECM remodeling, while others focus on miRNAs regulating inflammation; risk factors such as smoking and hypertension further increase vascular wall stress and aneurysm growth. The lack of detailed understanding limits the development of targeted therapies and individual risk assessments. Risk-prediction models are promising; however these models require further external validation to ensure reliability and clinical applicability. Personalized approaches integrating biomechanics and advanced imaging may improve rupture risk assessment. However, trials of antibiotics and renin-angiotensin system inhibitors have shown limited benefit. Observational studies have suggested potential benefits of metformin and statins. Preclinical studies have proposed that targeting inflammatory pathways such as the NOD-like receptor P3 inflammasome is a novel therapeutic strategy to mitigate aneurysm progression. Furthermore, innovative nanoparticle-based drug delivery systems have been explored to deliver matrix metalloproteinase inhibitors directly to the aneurysm site to prevent aneurysm expansion while minimizing systemic side effects. Integrative research is urgently needed to clarify AAA progression, improve outcomes, and enable personalized detection of high-risk subthreshold AAAs while avoiding overtreatment of low-risk cases. This review consolidates current knowledge on AAA pathophysiology, epidemiology, and treatment challenges.