Colchicine Does Not Reduce Abdominal Aortic Aneurysm Growth in a Mouse Model

• Main Authors: James Phie (Author), Shivshankar Thanigaimani (Author), Pacific Huynh (Author), Raghuveeran Anbalagan (Author), Corey S. Moran (Author), Robert Kinobe (Author), Joseph V. Moxon (Author), Matt A. Field (Author), Smriti M. Krishna (Author), Jonathan Golledge (Author)
• Format: Book
• Published: Hindawi-Wiley, 2022-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1755-5922; 10.1155/2022/5299370
• Keywords: Therapeutics. Pharmacology; RM1-950; Diseases of the circulatory (Cardiovascular) system; RC666-701
• Source: Cardiovascular Therapeutics, Vol 2022 (2022)

Background and Aims. The nacht domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome is upregulated in human abdominal aortic aneurysm (AAA), but its pathogenic role is unclear. The aims of this study were firstly to examine whether the inflammasome was upregulated in a mouse model of AAA and secondly to test whether the inflammasome inhibitor colchicine limited AAA growth. Methods. AAA was induced in eight-week-old male C57BL6/J mice with topical application of elastase to the infrarenal aorta and oral 3-aminopropionitrile (E-BAPN). For aim one, inflammasome activation, abdominal aortic diameter, and rupture were compared between mice with AAA and sham controls. For aim two, 3 weeks after AAA induction, mice were randomly allocated to receive colchicine (n=28, 0.2 mg/kg/d) or vehicle control (n=29). The primary outcome was the rate of maximum aortic diameter increase measured by ultrasound over 13 weeks. Results. There was upregulation of NLRP3 markers interleukin- (IL-) 1β (median, IQR; 15.67, 7.11-22.60 pg/mg protein versus 6.87, 4.54-11.60 pg/mg protein, p=.048) and caspase-1 (109, 83-155 relative luminosity units (RLU) versus 45, 38-65 RLU, p<.001) in AAA samples compared to controls. Aortic diameter increase over 80 days (mean difference, MD, 4.3 mm, 95% CI 3.3, 5.3, p<.001) was significantly greater in mice in which aneurysms were induced compared to sham controls. Colchicine did not significantly limit aortic diameter increase over 80 days (MD -0.1 mm, 95% CI -1.1, 0.86, p=.922). Conclusions. The inflammasome was activated in this mouse model of AAA; however, daily oral administration of colchicine did not limit AAA growth.