Mechanistic Justification for Pentagalloyl Glucose Mediated AAA Suppression

Project: CSA

Investigators

  • Ender A Finol (CoI)
  • Dan T Simionescu (CoI)
  • Satish Chandra Muluk (CoI)

Description

Penta-galloyl glucose (PGG) is a unique non-cytotoxic elastin-binding agent that stabilizes elastin and collagen in the aorta, protecting them from the destructive action of extracellular matrix degrading enzymes, thereby inhibiting progression of abdominal aortic aneurysm (AAA). The significance of this research lies in our ability to characterize the AAA biomechanical environment after PGG application through integration of state-of-the-art optical and magnetic resonance imaging with computational modeling. This will provide a mechanical justification for PGG-induced AAA suppression, yielding early evidence of PGG's role in future clinical studies. The overall goal of this proposal is to evaluate the biomechanical potential for PGG to inhibit AAA growth in an in vivo model. We hypothesize that the application of PGG to the diseased abdominal aorta will suppress AAA peak wall stress without interfering with the inflammatory mechanisms typical of aneurysmal disease. We propose to address this hypothesis by quantifying vessel inflammatory markers and image-based peak wall stress in the established elastase induced AAA mouse model. To this end, we will develop an experimental design based on six animal groups (90 subjects total). The following Specific Aims shall be completed to address the aforementioned hypothesis: (1) Evaluate AAA wall stress based on micro-magnetic resonance imaging (MRI); (2) Estimate local inflammatory activity and abdominal aorta tissue properties; and (3) Assess the time-progression of wall stress and inflammatory activity. The primary expected outcomes of this research are the differences in mechanical properties and peak wall stress between the prevention and suppression groups due to the stabilization of elastin and collagen, thereby inferring that PGG could be an effective therapy for AAA rupture risk decrease.
Award amount$750,000.00
Award date07/01/2016
Program typeCollaborative Sciences Award
Award ID16CSA28480006
Effective start/end date07/01/201606/30/2019
StatusFinished