Colchicine ameliorates short-term abdominal aortic aneurysms by inhibiting the expression of NLRP3 inflammasome components in mice

Background Abdominal aortic aneurysms (AAA) are often associated with chronic inflammation and pose a significant risk to affected individuals. Colchicine, known for its anti-inflammatory properties, has shown promise in managing cardiovascular diseases. However, its specific role in the development of AAA remains poorly understood. Methods and results In this study, we employed a short-term AAA model induced by angiotensin II (Ang II, 1000?ng/kg/min) and calcium chloride (CaCl 2 , 0.5?mol/l) in male ApoE -/- and C57BL/6 mice (8–12 weeks old) to investigate the effects of colchicine on AAA progression. Colchicine (0.4?mg/kg) was administered orally once daily, starting on the same day as AAA induction. After a 4-week duration, we observed a significant reduction in AAA diameter, degradation of elastic fibers, and expression of components related to the Nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome in the vessel wall of colchicine-treated mice compared to the saline group. Mechanistically, colchicine (5?μm/l, for 24h) inhibited the expression of NLRP3 inflammasome components through the P38-ERK/MicroRNA145-toll-like receptor 4 (TLR4) pathway in RAW264.7?cells. Conclusions Our study demonstrates the effectiveness of colchicine in suppressing NLRP3 inflammasome components, thereby delaying AAA progression in the Ang II and CaCl 2 -induced short-term model. These findings suggest the potential of colchicine as a pharmacological treatment option for AAA.

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