| First Author | Salmon M | Year | 2022 |
| Journal | Ann Vasc Surg | Volume | 85 |
| Pages | 358-370 | PubMed ID | 35680012 |
| Mgi Jnum | J:335010 | Mgi Id | MGI:7461341 |
| Doi | 10.1016/j.avsg.2022.05.024 | Citation | Salmon M, et al. (2022) Genetic and Pharmacological Disruption of Interleukin-1alpha Leads to Augmented Murine Aortic Aneurysm. Ann Vasc Surg 85:358-370 |
| abstractText | BACKGROUND: Interleukin-1 (IL-1) signaling has an established role as a cytokine signaling pathway important for progression of abdominal aortic aneurysms (AAAs). While the IL-1beta ligand and IL-1R1 have been previously investigated, the role of the IL-1alpha ligand in AAAs remains unknown. In this study, we sought to examine the role of IL-1alpha in AAAs using genetic and pharmacologic approaches. METHODS: Eight-week-old wild-type (WT) or IL-1alpha knock-out (KO) male and female mice (n = 10-16/group) underwent experimental AAA and were harvested 14 days following surgery to assess AAA size and characteristics. In separate studies, 8-week-old WT mice were treated with an inhibitor to IL-1alpha during AAA formation and harvested 14 days following surgery. Finally, WT and IL-1alpha KO mice were administered Anakinra, an IL-R1 inhibitor, during AAA formation to determine the effect of inhibiting IL-1R1 when IL-1alpha is knocked out. RESULTS: Male and female IL-1alpha KO mice had larger AAAs compared to WT AAAs (male: 153% vs. 89.2%, P = 0.0001; female: 86.6% vs. 63.5%, P = 0.02). IL-1alpha KO mice had greater elastin breakage (P = 0.01), increased levels of macrophage staining (P = 0.0045), and greater pro-metallo proteinase 2 (P = 0.02). Pharmacologic inhibition of WT male mice with an IL-1alpha neutralizing antibody resulted in larger AAAs (133.1% vs. 77.0%, P < 0.001). Finally, treatment of IL-1alpha KO male mice with Anakinra decreased AAA formation compared with vehicle control AAAs (Anakinra + IL-1alpha KO: 47.7% vs. WT: 147.1%; P = 0.0001). CONCLUSIONS: IL-1alpha disruption using either genetic or pharmacologic approaches worsens AAAs. |
