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Proteolytic destruction of aortic extracellular matrix 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 extracellular matrix stabilization. We investigated the effectiveness of this treatment in limiting experimental AAA progression.
Methods
AAAs were created in 8- to 10-week-old male C57BL/6J mice via intra-aortic elastase infusion. Natural vascular scaffolding (2 mg/mL, Alucent Biomedical, Salt Lake City, UT) 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 humane killing.
Results
Ultrasound examination confirmed progressive aortic enlargement and AAA formation in all vehicle-treated mice within 14 days following elastase infusion. Natural vascular scaffolding 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.
Conclusions
Photochemical linking of extracellular matrix proteins attenuated experimental AAA progression, suggesting a potential translational application for this approach in clinical disease management.
Author Disclosures: B. Xu: Nothing to disclose; T. Ikezoe: Nothing to disclose; J. Guo: Nothing to disclose; T. Shoji: Nothing to disclose; K. S. Warner: Employment, Alucent Biomedical; K. Kauser: Employment, Alucent Biomedical; R. L. Dalman: Nothing to disclose
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