Cycloastragenol Inhibits Experimental Abdominal Aortic Aneurysm Progression

Leander Gaarde Melin, Julie Husted Dall, Jes S. Lindholt, Lasse Bach Steffensen, Hans Christian Beck, Sophie L. Elkrog, Pernille Duus Clausen, Lars Melholt Rasmussen, Jane Stubbe

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Abstract

The pathogenesis of abdominal aortic aneurysm involves vascular inflammation and elastin degradation. Astragalus radix contains cycloastragenol, which is known to be anti-inflammatory and to protect against elastin degradation. We hypothesized that cycloastragenol supplementation inhibits abdominal aortic aneurysm progression. Abdominal aortic aneurysm was induced in male rats by intraluminal elastase infusion in the infrarenal aorta and treated daily with cycloastragenol (125 mg/kg/day). Aortic expansion was followed weekly by ultrasound for 28 days. Changes in aneurysmal wall composition were analyzed by mRNA levels, histology, zymography and explorative proteomic analyses. At day 28, mean aneurysm diameter was 37% lower in the cycloastragenol group (p < 0.0001). In aneurysm cross sections, elastin content was insignificantly higher in the cycloastragenol group (10.5% ± 5.9% vs. 19.9% ± 16.8%, p = 0.20), with more preserved elastin lamellae structures (p = 0.0003) and without microcalcifications. Aneurysmal matrix metalloprotease-2 activity was reduced by the treatment (p = 0.022). Messenger RNA levels of inflammatory-and anti-oxidative markers did not differ between groups. Explorative proteomic analysis showed no difference in protein levels when adjusting for multiple testing. Among proteins displaying nominal regulation were fibulin-5 (p = 0.02), aquaporin-1 (p = 0.02) and prostacyclin synthase (p = 0.007). Cycloastragenol inhibits experimental abdominal aortic aneurysm progression. The suggested underlying mechanisms involve decreased matrix metalloprotease-2 activity and preservation of elastin and reduced calcification, thus, cycloastragenol could be considered for trial in abdominal aortic aneurysm patients.

Original languageEnglish
Article number359
JournalBiomedicines
Volume10
Issue number2
ISSN2227-9059
DOIs
Publication statusPublished - Feb 2022

Keywords

  • Aortic aneurysm
  • Drug delivery
  • Experimental model
  • Pathogenesis
  • Pharmacological therapy

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