Abdominal aortic aneurysms (AAAs) are associated with impaired arterial wall integrity, leading to abnormal ballooning and eventual fatal rupture. Currently the sole treatment for such aneurysms is surgical intervention. Surgical procedures entail either endovascular stent graft repair or complete replacement of the diseased arterial segment with an artificial vascular graft. Although often effective, endovascular stents are anatomically appropriate for only 30% to 60% of AAA patients at the outset and present the risk of endoleaks and graft displacement. Moreover, open surgery for full size graft insertion is highly invasive, making it inappropriate for patients with high operative risk. The drawbacks associated with these procedures are significant enough that they are only applied to those patients with late-stage, critical aneurysms. Treatment options are particularly limited (virtually non-existent) for patients with small or moderate aneurysms, which comprise the largest percentage of all aneurysm patients. Consequently, novel therapeutic approaches targeted at hindering the progression of aneurysms promptly after diagnosis would be extremely beneficial. By halting the aneurysm-related expansion or growth, the risk of rupture could be significantly decreased. In addition to arterial dilatation, the onset and progression of AAAs are associated with enzymatic degradation of extracellular matrix components such as elastin. Phenolic tannins, such as penta-galloylglucose (PGG), bind to vascular elastin, and in doing so, render elastin highly resistant to enzymatic degeneration while also making the tissue mechanically stronger. These unique properties provide a platform for the potential development of novel, safe, and effective treatments for all AAAs. In previous studies, we have shown that PGG binds to aortic tissue, protects extracellular matrix proteins such as elastin, mechanically strengthens the tissue, and is effective in stopping aneurysm growth/development in a widely accepted animal model. This proposal describes the development of endovascular tools to deliver this treatment locally to the site of aneurysm (from inside the blood vessel). For the work proposed here, we will evaluate the ability of our devices to deliver the aforementioned stabilizing agents to an isolated area of aortic aneurysmal disease. The tools and delivery procedure will be carried out in an endovascular and minimally invasive fashion. Evaluation of three distinct device prototypes will initially be performed in vitro with physiologically relevant silicon models. Upon selection of the superior device prototype, this particular design will also be evaluated in vivo. For these studies, the device will be deployed to isolate a region of porcine infrarenal abdominal aorta, allowing PGG to be delivered to this specific region. Subsequent analysis will evaluate the binding of PGG to the local aortic wall, and its effect on this tissue.
Abdominal aortic aneurysms (AAAs) progressively grow over a period of years and pose great health risks as a result of the potential to rupture, which can be fatal in >80% of cases. AAAs are apparently increasing in frequency and are a serious health concern for the aging population, among the top 10 causes of death for older men. The goal is to develop a minimally invasive treatment for AAAs which would hinder the progression or growth of this life-threatening disease, subsequently reducing the risk of rupture and positively impacting thousands of patients.
