Perivascular adipokine signaling in abdominal aortic aneurysm: cardiometabolic drivers of vascular remodeling and translational opportunities

Abdominal aortic aneurysm (AAA) represents a significant vascular pathology characterized by high mortality rates and a paucity of effective pharmacological interventions. Recent research underscores the role of perivascular adipose tissue derived adipokines in establishing a direct connection between obesity and the pathogenesis of AAA. These adipokines exert influence on aneurysmal remodeling by modulating the functions of vascular cells, particularly in relation to inflammation and extracellular matrix degradation. They can be categorized into two broad classes: deleterious (pro-aneurysmal) and protective (anti-aneurysmal). Deleterious adipokines exacerbate AAA through the promotion of inflammation, the weakening of the vascular wall, and the stimulation of aberrant vascular growth. In contrast, protective adipokines contribute to the attenuation of AAA progression via antioxidative, anti-inflammatory, and vascular homeostatic mechanisms. Recent evidence indicates that restoring adipokine balance may serve as a promising therapeutic approach for AAA. Although the majority of studies are still in the preclinical stage, the repurposing of metabolic drugs such as GLP-1 receptor agonists, metformin, and PPAR agonists has shown potential in rebalancing adipokine profiles, reducing inflammation, and promoting vascular repair. Additionally, novel agents targeting adipokine receptors, including adiponectin agonists, chemerin antagonists, and FABP4 inhibitors, have demonstrated preliminary efficacy in modulating adipokine signaling and mitigating vascular inflammation. This review synthesizes the mechanistic roles of adipokines in AAA, with a focus on therapeutic opportunities targeting adipokine driven pathways, and outlines a framework for future translational and clinical research aimed at adipokine-based management of AAA.