| First Author | Suehiro C | Year | 2019 |
| Journal | Atherosclerosis | Volume | 289 |
| Pages | 14-20 | PubMed ID | 31445353 |
| Mgi Jnum | J:293641 | Mgi Id | MGI:6453108 |
| Doi | 10.1016/j.atherosclerosis.2019.08.003 | Citation | Suehiro C, et al. (2019) Deletion of interleukin-18 attenuates abdominal aortic aneurysm formation. Atherosclerosis 289:14-20 |
| abstractText | 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 beta-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 (p<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. |
