Intraluminal infusion of Penta-Galloyl Glucose reduces abdominal aortic aneurysm development in the elastase rat model

Abstract

Background

An abdominal aortic aneurysm (AAA) is a progressive chronic dilatation of the abdominal aorta with terminally rupture when the aortic wall is so weakened that aortic wall stress exceeds wall strength. No effective medical treatment exists so far. We aimed to test whether intraluminal admission of Penta-Galloyl Glucose (PGG) treatment in a rodent AAA model could hold the potential to inhibit aneurysmal progression.

Method

Male Sprague Dawley rats had either intraluminal elastase infused for AAA induction or saline to serve as controls. In two independent experimental series, elastase was used to induce AAA followed by an intraluminal PGG (directly or by a drug eluting balloon) treatment. All rats were followed for 28 days and euthanized. In both series, maximal infrarenal aortic diameter was measured at baseline and at termination as a measure of AAA size. In series 2, maximal internally AAA diameter was followed by ultrasound weekly. AAA tissues were analyzed for elastin integrity by millers stain, collagen deposition by masson trichrome staining. In other AAA tissue samples the mRNA level of CD45, lysyloxidase (LOX), lysyloxidase like protein 1 (LOXL1) were determined by qPCR.

Results

Direct administration of PGG significantly reduced AAA expansion when compared to controls. PGG treatment resulted in a higher number and more preserved elastic fibers in the aneurysmal wall, while no significant difference was seen in the levels of CD45 and LOX mRNA levels. The drug eluting balloon (DEB) experiment showed no significant difference in AAA size observed neither macroscopically nor ultrasonically. Also the aneurysmal mRNA levels of CD45, LOX and LOXL1 were unchanged between groups.

Conclusion

A significant reduced expansion of AAAs was observed in the PGG group, suggesting PGG as a drug to inhibit aneurysmal progression, while administration through a DEB did not show a promising new way of administration.