Since then, multiple studies have investigated nanoparticle-based PGG delivery to the site of AAA. Isenberg and colleagues applied PGG periadventitially to the abdominal aorta of adult male Sprague–Dawley rats, previously exposed to CaCl 2-mediated aortic elastin injury, and found that early inhibition of aneurysm and stabilization of elastin lamellae is possible. PGG has multiple phenolic hydroxyl groups that have high affinity towards the hydrophobic regions of the tissues and can bind to proline-rich proteins such as elastin and collagen by surface adsorption mechanisms. PGG has been shown to bind to elastin and collagen, and stabilizes the ECM. We envision the use of pentagalloyl glucose (PGG), a multifunctional polyphenol, as a potential pharmacological agent for AAA suppression. This multifaceted presentation of the disease makes the discovery of potential pharmacological targets a complex one (i.e., it has to consider the biological factors, the biomechanical environment, and the presence of ILT as a potential transport barrier).Īnti-inflammatory or matrix metalloproteinase inhibiting chemicals are the primary choice for stabilizing the aortic extracellular matrix (ECM). In addition, most aneurysms exhibit an intraluminal thrombus (ILT), which is also a source of proteolytic activity, increased wall weakening, and a preferential site for rupture. Disease progression is characterized by an increase in matrixmetalloproteinase (MMP) activity, which subsequently yields elevated wall stress and concomitantly higher wall stress to strength ratios. With the deficiency in elastin, collagen dominates the ECM. Increased elastase activity leads to disorganized and tortuous elastin fibers, which represents a compromised organization of load bearing proteins, resulting in reduced aortic elasticity, and further weakening of the aortic wall. Of the numerous etiological theories of AAA pathology, the degraded ECM theory is the widely accepted one, as human AAA specimens usually exhibit a reduction in elastin content and elastin crosslinking, and an increase in collagen crosslinking. The etiology of abdominal aortic aneurysm (AAA) development is believed to be multi-factorial, in that (i) the pathology is initiated at the molecular level (protease- and enzyme-related) (ii) it builds up to the tissue level through extracellular matrix (ECM) and structural changes and (iii) it manifests as geometrical-, biomechanical-, and blood flow-related alterations in the abdominal aorta, resulting in rupture if left untreated. PGG is a beneficial polyphenol that can be potentially translated to clinical practice for preventing rupture of the aneurysmal arterial wall. PGG binds to the hydrophobic core of arterial tissues and the crosslinking of ECM fibers is one of the possible explanations for the recovery of biomechanical properties observed in this study. Tensile moduli in the circumferential direction was found to be in descending order as N > P > E (195.6 ± 58.72 kPa > 81.8 ± 22.76 kPa > 46.51 ± 15.04 kPa p = 0.0314), whereas no significant differences were found in the longitudinal direction ( p = 0.1607). The maximum tensile stress of the N group was higher than that in both E and P groups for both circumferential (43.78 ± 14.18 kPa vs. An Ogden material model was fitted to the stress–strain data and finite element computational analyses of simulated native aorta and aneurysmal abdominal aorta were performed. Planar biaxial tensile testing was performed for native (N), enzyme-treated (collagenase and elastase) (E), and PGG (P) treated porcine abdominal aorta specimens (n = 6 per group). The objective of this study was to quantify pentagalloyl glucose (PGG) mediated biomechanical restoration of degenerated extracellular matrix (ECM).
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