Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Pharmacy, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China.
Clin Sci (Lond). 2023 Oct 11;137(19):1533-1545. doi: 10.1042/CS20230499.
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.
腹主动脉瘤(AAA)的特征是肾下主动脉至少扩张 1.5 倍,AAA 破裂是危及生命的。秋水仙碱是一种用于治疗痛风和家族性地中海热的药物,最近被批准用于降低已患有动脉粥样硬化疾病的成年患者发生心血管事件的风险。本研究采用猪胰弹性蛋白酶(PPE)和β-氨基丙腈(BAPN)处理建立 AAA 小鼠模型,旨在探讨秋水仙碱是否可以预防 AAA 的发生。结果表明,秋水仙碱可以限制 AAA 的形成,表现为主动脉总重量/体重降低、AAA 发生率、最大腹主动脉直径和胶原沉积减少。还发现秋水仙碱可以防止 AAA 期间血管平滑肌细胞从收缩型向合成型的表型转换。此外,研究表明秋水仙碱能够减少 AAA 小鼠模型中血管炎症、氧化应激、细胞焦亡和免疫细胞浸润到主动脉壁。最后,证明秋水仙碱对 AAA 形成的保护作用主要是通过防止免疫细胞浸润到主动脉壁来介导的。总之,这些发现表明秋水仙碱可以预防实验性 AAA 的发生,为临床 AAA 干预提供了一种潜在的治疗策略。