Abstract 345: Natural Vascular Scaffolding Suppresses Experimental Abdominal Aortic Aneurysms

Abstract

Objective: Proteolytic destruction of aortic extracellular matrix (ECM) is central to abdominal aortic aneurysm (AAA) pathogenesis. Matrix metalloproteinase inhibition with doxycycline failed to limit AAA progression. However, photochemical modification of collagen and elastin fibers may provide an alternative approach to ECM stabilization. We investigated the effectiveness of this treatment in limiting experimental AAA progression. Methods: AAAs were created in 8-10 weeks old male C57BL/6J mice via intra-aortic elastase infusion. Natural vascular scaffolding (NVS) (2 mg/ml, Alucent Biomedical) or vehicle solution was applied to the abluminal aortic wall immediately following elastase infusion and aortotomy closure and exposed to laser light activation. AAA progression was assessed via serial ultrasound aortic diameter measurements and histopathologic analysis at sacrifice. Results: Ultrasonography confirmed progressive aortic enlargement and AAA formation in all vehicle-treated mice within 14 days following elastase infusion. NVS treatment substantially attenuated AAA development and progression with reduced medial elastin degradation and smooth muscle cell depletion, as well as mural neovessel development. No difference was seen in aortic CD4 or CD8 T accumulation between the two treatment groups. Conclusion: Photochemical linking of extracellular matrix proteins attenuated experimental AAA progression, suggesting a potential translational application for this approach in clinical disease management.