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

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...

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Main Authors: James Phie, Shivshankar Thanigaimani, Pacific Huynh, Raghuveeran Anbalagan, Corey S. Moran, Robert Kinobe, Joseph V. Moxon, Matt A. Field, Smriti M. Krishna, Jonathan Golledge
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Cardiovascular Therapeutics
Online Access:http://dx.doi.org/10.1155/2022/5299370
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author James Phie
Shivshankar Thanigaimani
Pacific Huynh
Raghuveeran Anbalagan
Corey S. Moran
Robert Kinobe
Joseph V. Moxon
Matt A. Field
Smriti M. Krishna
Jonathan Golledge
author_facet James Phie
Shivshankar Thanigaimani
Pacific Huynh
Raghuveeran Anbalagan
Corey S. Moran
Robert Kinobe
Joseph V. Moxon
Matt A. Field
Smriti M. Krishna
Jonathan Golledge
author_sort James Phie
collection DOAJ
description 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.
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series Cardiovascular Therapeutics
spelling doaj-art-f0438e47bfaf4b59bbf4528f263c5c342025-02-03T05:57:24ZengWileyCardiovascular Therapeutics1755-59222022-01-01202210.1155/2022/5299370Colchicine Does Not Reduce Abdominal Aortic Aneurysm Growth in a Mouse ModelJames Phie0Shivshankar Thanigaimani1Pacific Huynh2Raghuveeran Anbalagan3Corey S. Moran4Robert Kinobe5Joseph V. Moxon6Matt A. Field7Smriti M. Krishna8Jonathan Golledge9The Vascular Biology UnitThe Vascular Biology UnitThe Vascular Biology UnitThe Vascular Biology UnitThe Vascular Biology UnitCollege of Public HealthThe Vascular Biology UnitAustralian Institute of Tropical Health & Medicine and Centre for Tropical Bioinformatics and Molecular BiologyThe Vascular Biology UnitThe Vascular Biology UnitBackground 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.http://dx.doi.org/10.1155/2022/5299370
spellingShingle James Phie
Shivshankar Thanigaimani
Pacific Huynh
Raghuveeran Anbalagan
Corey S. Moran
Robert Kinobe
Joseph V. Moxon
Matt A. Field
Smriti M. Krishna
Jonathan Golledge
Colchicine Does Not Reduce Abdominal Aortic Aneurysm Growth in a Mouse Model
Cardiovascular Therapeutics
title Colchicine Does Not Reduce Abdominal Aortic Aneurysm Growth in a Mouse Model
title_full Colchicine Does Not Reduce Abdominal Aortic Aneurysm Growth in a Mouse Model
title_fullStr Colchicine Does Not Reduce Abdominal Aortic Aneurysm Growth in a Mouse Model
title_full_unstemmed Colchicine Does Not Reduce Abdominal Aortic Aneurysm Growth in a Mouse Model
title_short Colchicine Does Not Reduce Abdominal Aortic Aneurysm Growth in a Mouse Model
title_sort colchicine does not reduce abdominal aortic aneurysm growth in a mouse model
url http://dx.doi.org/10.1155/2022/5299370
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