Related Experiment Video
Updated: May 10, 2026
Murine Model of Thoracic Aortic Dissection Induced by Oral β-Aminopropionitrile and Subcutaneous Angiotensin II Infusion
Published on: May 16, 2025
Protective effects of selective mineralocorticoid receptor antagonist against aortic aneurysm progression in a novel
Hirotsugu Kurobe1, Yoichiro Hirata, Yuki Matsuoka
1Department of Cardiovascular Surgery, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
Background:
The optimal medical management to delay the progression of aortic aneurysms has not been fully clarified, and the only standard treatment at present is antihypertensive therapy. Previous studies have shown beneficial effects of selective mineralocorticoid receptor (MR) antagonists on cardiovascular remodeling. The aim of the present study was to investigate the effect of a selective MR antagonist on aortic aneurysm progression.
Methods:
Seven-week-old C57BL/6J male mice were administered with angiotensin II and β-aminopropionitrile for 4 weeks. The mice received either vehicle or eplerenone, a selective MR antagonist (100 mg/kg daily) every day by gavage, starting at 7 weeks of age. The production of inflammatory cytokines in cultures of high mobility group box-1-stimulated macrophages with or without a MR antagonist was also analyzed using an enzyme-linked immunosorbent assay.
Results:
Although no differences were found in the peak systolic blood pressure between the experimental groups, the mice in the eplerenone group showed a significant reduction in aneurysm development. On histologic analysis, coarse and stretched elastic fibers were markedly improved in the aortic wall in the eplerenone group. Real-time polymerase chain reaction of both aortic wall and perivascular adipose tissue demonstrated the expression of tumor necrosis factor-α, interleukin-6, and matrix metalloproteinase-2 was significantly decreased in eplerenone group, and that of monocyte chemoattractant protein-1 in the aortic wall was also significantly decreased. Macrophage infiltration in the aortic wall and perivascular adipose tissue in the eplerenone group was also significantly decreased. The production of tumor necrosis factor-α and interleukin-6 in macrophage culture, which was stimulated by high mobility group box-1 and CpG oligodeoxynucleotides, was also significantly decreased in the eplerenone group.
Conclusions:
Eprelenone suppressed aortic aneurysm progression through an anti-inflammatory effect. Thus, selective MR antagonists might be effective in preventing the progression of aortic aneurysms.
Insights
Selective mineralocorticoid receptor (MR) antagonists like eplerenone may prevent aortic aneurysm progression. Eplerenone reduced aneurysm development by suppressing inflammation, offering a potential new treatment strategy.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Medical Science
Background:
- Aortic aneurysm progression management remains unclear, with antihypertensive therapy as the current standard.
- Selective mineralocorticoid receptor (MR) antagonists have shown promise in mitigating cardiovascular remodeling.
Purpose of the Study:
- To investigate the efficacy of a selective MR antagonist, eplerenone, in preventing aortic aneurysm progression.
Main Methods:
- Mice were induced with angiotensin II and β-aminopropionitrile to develop aortic aneurysms.
- Eplerenone (100 mg/kg daily) or vehicle was administered orally for 4 weeks.
- Inflammatory cytokine production in macrophages was analyzed via ELISA.
Main Results:
- Eplerenone significantly reduced aneurysm development without altering blood pressure.
- Histological analysis revealed improved elastic fibers in the aortic wall of the eplerenone group.
- Eplerenone decreased inflammatory markers (TNF-α, IL-6, MMP-2, MCP-1) and macrophage infiltration in aortic and adipose tissues.
Conclusions:
- Eplerenone suppresses aortic aneurysm progression via anti-inflammatory mechanisms.
- Selective MR antagonists represent a potential therapeutic approach for preventing aortic aneurysm expansion.
