Deletion of interleukin-18 attenuates abdominal aortic aneurysm formation


      • IL-18 deletion attenuated abdominal aortic aneurysm (AAA) formation.
      • IL-18 induced enhanced expression of osteopontin in vascular smooth muscle cells.
      • IL-18 contributes to inflammation and matrix metalloproteinase activation in AAA.


      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−/− 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).


      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.

      Graphical abstract


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