Dexamethasone Inhibits Abdominal Aortic Aneurysm Progression in Rats, though with Major Catabolic Effects

Introduction: Abdominal aortic aneurysm is a chronic local dilatation of the abdominal aorta, and it is responsible of numerous deaths annually in elderly males, when the aneurysm ruptures. There is no medical treatment to prevent AAA progression. The pathogenesis of AAA is not well characterized. One of the main drivers of the disease is chronic vascular inflammation.

Aim: we hypothesize that dexamethasone known for its anti-inflammatory properties and used to treat other patient group with long term, could be used to prevent AAA expansion.

Methods and Results: In male Sprague-Dawley rats AAA was induced by intraluminal porcine pancreas elastase infusion in the infra renal region. The following day dexamethasone treatment was initiated by gavage in either 0.1 mg/kg/day (n=13) or 0.1 mg/kg (n=15) every other day, or saline control (n=19) for 9-14 days. AAA expansion was significantly reduced in low dose dexamethasone (LDD, 41.4±14.9%) and high dose dexamethasone (HDD, 50.2±41.9%) compared to controls (116.8 ±64.9%, p<0.0002) determined by ultrasound measurements. As dexamethasone reduced body weighs up to 20% HDD was euthanized at day 10 (mean body weight:285.4±14.3g) while LDD continues until day 14 (332.9±16.3g) with a subset of the controls (366.1±20.4g/404±11.7g). Body composition by DEXA scans on post-surgery day 14, showed no change in bone mineral content (p=0.64) nor bone density (p<0.07), while body fat significantly decreased in the LDD group compared to control (39,5±9.2g vs.27.0 ±4.4g, n=6,13, p<0.03) and lean body mass (274.6±11.7g vs.327.7±12.2g, p<0.0001). Histological assessment of aneurysm cross sections showed no difference in elastin content by Millers staining(p=0.28) nor in infiltration neutrophils, (myeloperoxidase positive cells, p=0.10) nor area of vascular smooth muscle cells (ACTA2 positive cells, p=0.14).

Conclusion: Dexamethasone can prevent AAA expansion but is associated with loss of body fat and lean body mass. Thus, it is not recommended as treatment option in the tested doses.

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Artikel online veröffentlicht:
11. Juni 2024