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.
Highlights
Microscopic analysis of HE-stained liver lobes displayed no obvious differences as evaluated by investigators
A total of four rats were excluded causing an unintendedly higher non-significant mean initial body weight in the vehicle treated rats when compared to the CAG-treated group
We have previously shown that loss of AQP1 accelerates angiotensin II-induced atherosclerosis in hyperlipidemic mice [29]
Summary
Abdominal aortic aneurysm (AAA) is a localized enlargement of the aorta exceeding. 3 cm in diameter and is potentially life-threatening [1]. AAA rupture is a major cause of mortality in elderly men, being responsible for the death of 1% of men above. 65 years [1,2]. Patients with known AAAs are carefully monitored and offered surgical repair when the AAA possesses a diameter above 5–6 cm. An urgent unmet clinical need of medical therapies for small AAAs exists, to prevent progressive dilatation, acute or elective surgical repair, rupture, and death [3,4,5]. An urgent unmet clinical need of medical therapies for small AAAs exists, to prevent progressive dilatation, acute or elective surgical repair, rupture, and death [3,4,5]. 4.0/).
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