Colchicine protects against the development of experimental abdominal aortic aneurysm

Abstract

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 beta 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.

Colchicine Blocks Abdominal Aortic Aneurysm Development by Maintaining Vascular Smooth Muscle Cell Homeostasis

“…When colchicine was given at late stage when AAA was already established, colchicine lost its inhibitory role 2 , 20 . In contrast, when colchicine was given at the first day of BAPN and elastase application combination-induced AAA, the same drug showed a potent a potent limitation of AAA growth 18 . We and others further demonstrated that early use of colchicine prevented AAA development and rupture in several AAA models, for example, Ang-II infusion, calcium chloride and calcium phosphate application 19 .…”

“…Studies reported that daily administration of colchicine did not significantly limit AAA growth 20 . Yet, evidence form us and those from others suggested a therapeutic role of colchicine on AAA 18 , 19 . Although we do not have exact explanation for these conflicting results, differences in AAA models and the time point of colchicine administration may account for these observations.…”

“…Controversial observations were existed in the effective of colchicine on AAA treatment 18 - 20 . Studies reported that daily administration of colchicine did not significantly limit AAA growth 20 .…”

“…Unexpectedly, colchicine was subsequently identified to emerge as an effective therapeutic agent in cardiovascular diseases and was approved by the U.S. Food and Drug Administration to use in adult patients with established atherosclerotic disease or with multiple risk factors for cardiovascular disease in June 2023 14 - 17 . Colchicine may also provide similar protective effects on AAA 18 , 19 . Yet, other study yielded the opposite conclusion that colchicine did not reduced AAA growth 20 .…”

Potential application of peripheral blood biomarkers in intracranial aneurysms

“…It showed success in preventing atherosclerotic cerebrovascular disease. Zhao et al ( 81 ) conducted an animal study that demonstrated the protective effect of colchicine against the development of experimental abdominal aortic aneurysms. However, Phie et al ( 82 ) suggested that colchicine lacked efficacy in reducing the growth of abdominal aortic aneurysms in a mouse model.…”