Colchicine protects against the development of experimental abdominal aortic aneurysm.
Colchicine protects against the development of experimental abdominal aortic aneurysm.
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DOI：
10.1042/cs20230499
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发表时间：
2023-10-11
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腹主动脉瘤（AAA）的特征是肾下主动脉扩大至少1.5倍，破裂的AAA是危及生命的。秋水仙碱是一种用于治疗痛风和家族性地中海热的药物，最近，它被批准用于降低患有动脉粥样硬化疾病的成年患者心血管事件的风险。通过猪胰腺弹性酶（PPE）和β-氨基丙腈（BAPN）处理的AAA小鼠模型，本研究旨在探讨秋水仙碱是否可以预防AAA的发生。在这里，我们发现秋水仙碱可以限制AAA的形成，这可以通过降低每体重总主动脉重量、AAA发生率、最大腹主动脉直径和胶原沉积来证明。我们还发现秋水仙碱可以阻止AAA小鼠模型中血管平滑肌细胞从收缩状态到合成状态的表型转换。此外，我们还发现秋水仙碱可以减少AAA小鼠模型中的血管炎症、氧化应激、细胞焦灭和免疫细胞向主动脉壁的浸润。最后证明秋水仙碱对AAA形成的保护作用主要是通过阻止免疫细胞向主动脉壁浸润来介导的。综上所述，我们的研究结果表明秋水仙碱可以预防实验性AAA的发展，为临床干预AAA提供了潜在的治疗策略。
Abdominal aortic aneurysm (AAA) is characterized by at least 1.5-fold enlargement of the infrarenal aorta, a ruptured AAA is life-threatening. Colchicine is a medicine used to treat gout and familial Mediterranean fever, and recently, it was approved to reduce the risk of cardiovascular events in adult patients with established atherosclerotic disease. With an AAA mice model created by treatment with porcine pancreatic elastase (PPE) and β-aminopropionitrile (BAPN), this work was designed to explore whether colchicine could protect against the development of AAA. Here, we showed that colchicine could limit AAA formation, as evidenced by the decreased total aortic weight per body weight, AAA incidence, maximal abdominal aortic diameter and collagen deposition. We also found that colchicine could prevent the phenotypic switching of vascular smooth muscle cells from a contractile to synthetic state during AAA. In addition, it was demonstrated that colchicine was able to reduce vascular inflammation, oxidative stress, cell pyroptosis and immune cells infiltration to the aortic wall in the AAA mice model. Finally, it was proved that the protective action of colchicine against AAA formation was mainly mediated by preventing immune cells infiltration to the aortic wall. In summary, our findings demonstrated that colchicine could protect against the development of experimental AAA, providing a potential therapeutic strategy for AAA intervention in the clinic.