Perspectives on the Role of Platelets and Antiplatelet Therapies in Murine Models of Abdominal Aortic Aneurysm

Abdominal aortic aneurysm (AAA) pathogenesis reflects a convergence of extracellular matrix degradation, thrombosis, and vascular inflammation (thromboinflammation), where platelets and the intraluminal thrombus (ILT) are implicated in playing central, stage-dependent roles. Beyond their traditional role in hemostasis, activated platelets are known to localize in ILT, releasing chemokines, proteases, and growth factors, which aid in recruiting leukocytes and may drive aneurysm expansion through matrix breakdown. Although preclinical models and tissue analyses suggest platelet adhesion receptors and chemokine interactions contribute to leukocyte influx and aneurysm progression, the availability of preclinical models that recapitulate ILT is limited, and overall translational evidence remains inconclusive. A crucial question is whether ILT acts as a mere bystander in AAAs or actively contributes to aneurysm growth and rupture. Notably, the only randomized controlled trial to date testing an antiplatelet agent (ticagrelor) demonstrated no effect on AAA growth, raising concerns that platelets may not be an appropriate AAA treatment target. The development of AAA models that consistently manifest ILT will be essential for determining the therapeutic potential of targeting platelet inflammatory functions (eg, glycoprotein VI signaling inhibition). Ultimately, clarifying whether ILT-driven platelet inflammation is a modifiable mechanism or a bystander signal will require ILT-specific models and rigorously powered trials to define safe, hemostasis-sparing antiplatelet strategies for AAA.