Deletion of interleukin-18 attenuates abdominal aortic aneurysm formation.
Atherosclerosis
; 289: 14-20, 2019 10.
Article
de En
| MEDLINE
| ID: mdl-31445353
ABSTRACT
BACKGROUND AND AIMS:
Abdominal aortic aneurysm (AAA) is a common disease; however, its exact pathogenesis remains unknown, and no specific medical therapies are available. Interleukin (IL)-18 plays a crucial role in atherosclerotic plaque destabilization and is a strong predictor of cardiovascular death. Here, we investigated the role of IL-18 in AAA pathogenesis using an experimental mouse model. METHODS ANDRESULTS:
After infusion of angiotensin II (Ang II) for 4 weeks and ß-aminopropionitrile (BAPN) for 2 weeks, 58% of C57/6J wild-type (WT) mice developed AAA associated with enhanced expression of IL-18; however, disease incidence was significantly lower in IL-18-/- mice than in WT mice (pâ¯<â¯0.01), although no significant difference was found in systolic blood pressure between WT mice and IL-18-/- mice in this model. Additionally, IL-18 deletion significantly attenuated Ang II/BAPN-induced macrophage infiltration, macrophage polarization into inflammatory M1 phenotype, and matrix metalloproteinase (MMP) activation in abdominal aortas, which is associated with reduced expression of osteopontin (OPN).CONCLUSIONS:
These findings indicate that IL-18 plays an important role in the development of AAA by enhancing OPN expression, macrophage recruitment, and MMP activation. Moreover, IL-18 represents a previously unrecognized therapeutic target for the prevention of AAA formation.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Anévrysme de l'aorte abdominale
/
Interleukine-18
Type d'étude:
Incidence_studies
/
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
Atherosclerosis
Année:
2019
Type de document:
Article
Pays d'affiliation:
Japon