Pentagalloyl Glucose (PGG) Partially Prevents Arterial Mechanical Changes Due to Elastin Degradation

Pavey, Shawn; Cocciolone, Austin J.; Marty, A; Ismail, Humza; Hawes, Jie Z; Wagenseil, Jessica E.

doi:10.1007/s11340-020-00625-1

Cited by 9 publications

(6 citation statements)

References 32 publications

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“…Moreover, our ex vivo data was largely in agreement with the in vivo data showing an improved change in circumferential strain even though both were measured at different reference configurations. By comparison, Patnaik et al 28 found a decrease in stiffness moduli with PGG treatments in a porcine model while Pavey et al 29 found stiffness to increase in an elastase-induced AAA mouse model. Although PGG has an obvious effect on vascular remodeling, the resultant mechanical properties appear to be treatment and disease model-specific 28 .…”

Section: Discussionmentioning

confidence: 99%

Systemic delivery of targeted nanotherapeutic reverses angiotensin II-induced abdominal aortic aneurysms in mice

Wang

Parasaram

Dhital

et al. 2021

Sci Rep

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Abdominal aortic aneurysm (AAA) disease causes dilation of the aorta, leading to aortic rupture and death if not treated early. It is the 14th leading cause of death in the U.S. and 10th leading cause of death in men over age 55, affecting thousands of patients. Despite the prevalence of AAA, no safe and efficient pharmacotherapies exist for patients. The deterioration of the elastic lamina in the aneurysmal wall is a consistent feature of AAAs, making it an ideal target for delivering drugs to the AAA site. In this research, we conjugated nanoparticles with an elastin antibody that only targets degraded elastin while sparing healthy elastin. After induction of aneurysm by 4-week infusion of angiotensin II (Ang II), two biweekly intravenous injections of pentagalloyl glucose (PGG)-loaded nanoparticles conjugated with elastin antibody delivered the drug to the aneurysm site. We show that targeted delivery of PGG could reverse the aortic dilation, ameliorate the inflammation, restore the elastic lamina, and improve the mechanical properties of the aorta at the AAA site. Therefore, simple iv therapy of PGG loaded nanoparticles can be an effective treatment option for early to middle stage aneurysms to reverse disease progression and return the aorta to normal homeostasis.

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Section: Discussionmentioning

confidence: 99%

Systemic delivery of targeted nanotherapeutic reverses angiotensin II-induced abdominal aortic aneurysms in mice

Wang

Parasaram

Dhital

et al. 2021

Sci Rep

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“…In addition, we have also demonstrated biomechanical recovery, via biaxial tensile testing, of PGG-treated porcine aortic tissue specimens that were previously degraded with elastase and collagenase in vitro [ 9 ]. Following this, Pavey et al reported in their in vitro study that prior PGG treatment of mouse carotid arteries prevented microstructural and mechanical damage by elastase, which was demonstrated by pressure-inflation testing [ 10 ]; however, they did not quantify the burst pressure of the specimens.…”

Section: Discussionmentioning

confidence: 99%

“…We gently separated the aorta from the inferior vena cava (IVC) and left the retroperitoneum on the IVC to ensure only the aorta was exposed to treatments. Initially, animals received a 15 min treatment of 0.3% PGG [ 8 , 10 ] or saline topically applied to the infrarenal aorta via gauze soaked in the solution. The PGG solution was made by dissolving 25 mg of PGG (Sigma Aldrich, St. Louis, MO, USA) in 8.33 mL of 0.9% NaCl.…”

Section: Methodsmentioning

confidence: 99%

“…Pentagalloyl glucose (PGG) is a polyphenolic compound that possesses the unique cross-linking ability to bind hydrophobic regions of collagen and elastin [ 7 ]. This cross-linking of extracellular matrix (ECM) proteins has led to a stabilized arterial microstructure of the abdominal aorta [ 8 ] and partial prevention of mechanical degradation in enzyme-treated arterial tissues [ 9 , 10 ]. Specifically, PGG has been utilized in rat [ 8 , 11 , 12 , 13 ], mice [ 14 ], and porcine [ 15 , 16 ] models of AAA to suppress the pathological expansion.…”

Section: Introductionmentioning

confidence: 99%

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Animal Model Dependent Response to Pentagalloyl Glucose in Murine Abdominal Aortic Injury

Anderson

Niedert

Patnaik

et al. 2021

JCM

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Abdominal aortic aneurysms (AAAs) are a local dilation of the aorta and are associated with significant mortality due to rupture and treatment complications. There is a need for less invasive treatments to prevent aneurysm growth and rupture. In this study, we used two experimental murine models to evaluate the potential of pentagalloyl glucose (PGG), which is a polyphenolic tannin that binds to and crosslinks elastin and collagen, to preserve aortic compliance. Animals underwent surgical aortic injury and received 0.3% PGG or saline treatment on the adventitial surface of the infrarenal aorta. Seventeen mice underwent topical elastase injury, and 14 mice underwent topical calcium chloride injury. We collected high-frequency ultrasound images before surgery and at 3–4 timepoints after. There was no difference in the in vivo effective maximum diameter due to PGG treatment for either model. However, the CaCl2 model had significantly higher Green–Lagrange circumferential cyclic strain in PGG-treated animals (p < 0.05). While ex vivo pressure-inflation testing showed no difference between groups in either model, histology revealed reduced calcium deposits in the PGG treatment group with the CaCl2 model. These findings highlight the continued need for improved understanding of PGG’s effects on the extracellular matrix and suggest that PGG may reduce arterial calcium accumulation.

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“…In vitro studies have suggested that PGG reduces oxidative stress and MMP secretion and improves the elastic properties of a myoblast cell line [22]. Ex vivo studies of the carotid arteries of mice suggest that PGG protected against elastase-induced artery destruction and limited the mechanical failure of the artery by repairing the elastic lamellae and limiting changes in the mechanical properties of the tissue [29]. A similar ex vivo study using pig aortic samples reported that PGG partially protected against elastase-and collagenase-induced biomechanical changes [30].…”

Section: Discussionmentioning

confidence: 99%

A Systematic Review and Meta-Analysis of the Effect of Pentagalloyl Glucose Administration on Aortic Expansion in Animal Models

2021

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Background: The aim of this systematic review was to pool evidence from studies testing if pentagalloyl glucose (PGG) limited aortic expansion in animal models of abdominal aortic aneurysm (AAA). Methods: The review was conducted according to the PRISMA guidelines and registered with PROSPERO. The primary outcome was aortic expansion assessed by direct measurement. Secondary outcomes included aortic expansion measured by ultrasound and aortic diameter at study completion. Sub analyses examined the effect of PGG delivery in specific forms (nanoparticles, periadventitial or intraluminal), and at different times (from the start of AAA induction or when AAA was established), and tested in different animals (pigs, rats and mice) and AAA models (calcium chloride, periadventitial, intraluminal elastase or angiotensin II). Meta-analyses were performed using Mantel-Haenszel’s methods with random effect models and reported as mean difference (MD) and 95% confidence intervals (CIs). Risk of bias was assessed with a customized tool. Results: Eleven studies reported in eight publications involving 214 animals were included. PGG significantly reduced aortic expansion measured by direct observation (MD: −66.35%; 95% CI: −108.44, −24.27; p = 0.002) but not ultrasound (MD: −32.91%; 95% CI: −75.16, 9.33; p = 0.127). PGG delivered intravenously within nanoparticles significantly reduced aortic expansion, measured by both direct observation (MD: −116.41%; 95% CI: −132.20, −100.62; p < 0.001) and ultrasound (MD: −98.40%; 95% CI: −113.99, −82.81; p < 0.001). In studies measuring aortic expansion by direct observation, PGG administered topically to the adventitia of the aorta (MD: −28.41%; 95% CI −46.57, −10.25; p = 0.002), studied in rats (MD: −56.61%; 95% CI: −101.76, −11.46; p = 0.014), within the calcium chloride model (MD: −56.61%; 95% CI: −101.76, −11.46; p = 0.014) and tested in established AAAs (MD: −90.36; 95% CI: −135.82, −44.89; p < 0.001), significantly reduced aortic expansion. The findings of other analyses were not significant. The risk of bias of all studies was high. Conclusion: There is inconsistent low-quality evidence that PGG inhibits aortic expansion in animal models.

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Pentagalloyl Glucose (PGG) Partially Prevents Arterial Mechanical Changes Due to Elastin Degradation

Cited by 9 publications

References 32 publications

Systemic delivery of targeted nanotherapeutic reverses angiotensin II-induced abdominal aortic aneurysms in mice

Systemic delivery of targeted nanotherapeutic reverses angiotensin II-induced abdominal aortic aneurysms in mice

Animal Model Dependent Response to Pentagalloyl Glucose in Murine Abdominal Aortic Injury

A Systematic Review and Meta-Analysis of the Effect of Pentagalloyl Glucose Administration on Aortic Expansion in Animal Models

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