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


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-) 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.

SUBMITTER: Phie J 

PROVIDER: S-EPMC9553691 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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

Phie James J   Thanigaimani Shivshankar S   Huynh Pacific P   Anbalagan Raghuveeran R   Moran Corey S CS   Kinobe Robert R   Moxon Joseph V JV   Field Matt A MA   Krishna Smriti M SM   Golledge Jonathan J  

Cardiovascular therapeutics 20220930


<h4>Background and aims</h4>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.<h4>Methods</h4>AAA was induced in eight-week-old male C57BL6/J mice with topical a  ...[more]

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