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Updated: Sep 20, 2025
Porcine Model of Infrarenal Abdominal Aortic Aneurysm
Published on: November 21, 2019
Genetic and Pharmacological Disruption of Interleukin-1α Leads to Augmented Murine Aortic Aneurysm
Morgan Salmon1, Robert B Hawkins2, Jolian Dahl3
1Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA; Department of Cardiac Surgery, University of Michigan School of Medicine, Ann Arbor, MI; Frankel Cardiovascular Center, University of Michigan School of Medicine, Ann Arbor, MI; Department of Surgery, Oschner Medical Center, New Orleans, LA.
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-1β ligand and IL-1R1 have been previously investigated, the role of the IL-1α ligand in AAAs remains unknown. In this study, we sought to examine the role of IL-1α in AAAs using genetic and pharmacologic approaches.
Methods:
Eight-week-old wild-type (WT) or IL-1α 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-1α during AAA formation and harvested 14 days following surgery. Finally, WT and IL-1α KO mice were administered Anakinra, an IL-R1 inhibitor, during AAA formation to determine the effect of inhibiting IL-1R1 when IL-1α is knocked out.
Results:
Male and female IL-1α 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-1α 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-1α neutralizing antibody resulted in larger AAAs (133.1% vs. 77.0%, P < 0.001). Finally, treatment of IL-1α KO male mice with Anakinra decreased AAA formation compared with vehicle control AAAs (Anakinra + IL-1α KO: 47.7% vs. WT: 147.1%; P = 0.0001).
Conclusions:
IL-1α disruption using either genetic or pharmacologic approaches worsens AAAs.
