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

Abstract

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.