Elastin stabilization for treatment of abdominal aortic aneurysms

Abstract

Conclusion: Administration of pentagalloyl glucose (PGG) in the periadventitial area of the aorta slows development of abdominal aortic aneurysm (AAA) in an animal model. Summary: Among other things, AAA is characterized by disruption or fragmentation of elastin and decreased medial elastin content. Treatment for AAA is surgical, and no pharmacologic therapy currently exists. In this article, the authors sought to explore the role of PGG, a potential elastin-stabilizing agent, for treatment of AAA. PGG is a polyphenolic tannin. Tannins bind to elastin and make them resistant to enzymatic degradation. The authors tested the ability of PGG to enhance elastin stability and interfere with AAA development in a well-established AAA model in rats that uses calcium chloride to mediate aortic injury and induce an AAA. In calcium chloride-induced aneurysms, the authors delivered PPG periadventitially at two separate time points during AAA development. They then measured aortic diameter, elastin integrity, and other pathologic markers in PGG-treated aortas compared with saline-treated control aortas. The periadventitial delivery of noncytotoxic levels of PGG inhibited elastin degeneration and attenuated AAA expansion. PPG hindered AAA development in the model without apparent effects on inflammation, calcification, and MMP activity. Despite high levels of proteinases from inflammatory cells in the wall of the aorta, PGG appeared to preserve the integrity of elastic lamina. Comment: Growth of AAAs appears to be associated with elastin degeneration secondary to proteinases derived from inflammatory cells infiltrating the aortic wall. By directly targeting what appears to be one of the primary biochemical mechanisms of AAA development, this article suggests a pharmacologic therapy for AAA. Refining delivery mechanisms and dosage intervals are obviously future areas of research in this field.