Colchicine Does Not Reduce Abdominal Aortic Aneurysm Growth in a Mouse Model
Phie, James, Thanigaimani, Shivshankar, Huynh, Pacific, Anbalagan, Raghuveeran, Moran, Corey S., Kinobe, Robert, Moxon, Joseph, Field, Matt A., Krishna, Smriti M., and Golledge, Jonathan (2022) Colchicine Does Not Reduce Abdominal Aortic Aneurysm Growth in a Mouse Model. Cardiovascular Therapeutics, 2022. 5299370.
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Abstract
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-) 1 beta (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.
Item ID: | 76690 |
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Item Type: | Article (Research - C1) |
ISSN: | 1755-5922 |
Copyright Information: | Copyright © 2022 James Phie et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Funders: | National Health and Medical Research Council (NHMRC) |
Projects and Grants: | NHMRC 1180736, NHMRC 1022752 |
Date Deposited: | 02 Nov 2022 08:44 |
FoR Codes: | 32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320101 Cardiology (incl. cardiovascular diseases) @ 100% |
SEO Codes: | 20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 100% |
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