Deletion of interleukin-18 attenuates abdominal aortic aneurysm formation.
Animals
Aorta, Abdominal
/ pathology
Aortic Aneurysm, Abdominal
/ genetics
Blood Pressure
Cell Proliferation
Gene Deletion
Incidence
Inflammation
Interleukin-18
/ genetics
Macrophages
/ metabolism
Male
Matrix Metalloproteinases
/ metabolism
Mice
Mice, Inbred C57BL
Muscle, Smooth, Vascular
/ metabolism
Osteopontin
/ metabolism
Phenotype
Systole
Abdominal aortic aneurysm
Interleukin-18
Macrophage
Matrix metalloproteinase
Osteopontin
Journal
Atherosclerosis
ISSN: 1879-1484
Titre abrégé: Atherosclerosis
Pays: Ireland
ID NLM: 0242543
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
15
11
2018
revised:
04
07
2019
accepted:
16
08
2019
pubmed:
25
8
2019
medline:
15
8
2020
entrez:
25
8
2019
Statut:
ppublish
Résumé
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. After infusion of angiotensin II (Ang II) for 4 weeks and β-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 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.
Sections du résumé
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 AND RESULTS
After infusion of angiotensin II (Ang II) for 4 weeks and β-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
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.
Identifiants
pubmed: 31445353
pii: S0021-9150(19)31437-6
doi: 10.1016/j.atherosclerosis.2019.08.003
pii:
doi:
Substances chimiques
Interleukin-18
0
Spp1 protein, mouse
0
Osteopontin
106441-73-0
Matrix Metalloproteinases
EC 3.4.24.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
14-20Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.