Colchicine Does Not Reduce Abdominal Aortic Aneurysm Growth in a Mouse Model.
Cardiovasc Ther
; 2022: 5299370, 2022.
Article
en En
| MEDLINE
| ID: mdl-36262119
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-) 1ß (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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Aneurisma de la Aorta Abdominal
Límite:
Animals
Idioma:
En
Revista:
Cardiovasc Ther
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
TERAPEUTICA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Australia