Abstract 98: Interleukin-1 Beta Deletion Protects Against Abdominal Aortic Aneurysm Development
Objectives: Inflammation is known to be critical in abdominal aortic aneurysm (AAA) formation. While interleukin-1 beta (IL-1B), a proinflammatory cytokine, is elevated in AAA samples from human and murine samples, the role of IL-1B during AAA formation remains largely unknown. We hypothesized that IL-1B is a significant positive contributor to the AAA inflammatory pathway.
Methods: Eight to 12 week old male mice deficient in the expression of IL-1B (IL-1B KO; n=9) and their corresponding wild type background mice (WT, n=5) underwent AAA induction by purified porcine elastase (0.4 units) infusion of the infrarenal aorta. After 14 days, the maximum diameter of the infrarenal abdominal aorta was measured, and the aortas were harvested for molecular and histologic analyses, including immunostaining for macrophages, neutrophils, and elastin. Inflammatory and smooth muscle genetic markers were compared using real-time PCR.
Results: IL-1B KO mice had significantly decreased aneurysm formation when compared to WT controls [34.2% aortic dilation versus 87.2% aortic dilation (p=0.002), respectively]. Immunostaining aortic cross-sections demonstrated markedly less macrophage and neutrophil infiltration of the aortic wall with preservation of elastic lamina in the aortas of IL-1B deficient mice. Genetic expression of inflammatory markers [matrix metalloproteinases (MMP) 2, 3, and 9] were decreased in the aortas from IL-1B KO mice compared to WT mice, while smooth muscle markers (i.e. smooth muscle actin, myosin heavy chain, and smooth muscle 22α) were all significantly greater in the aortas from IL-1B KO group.
Conclusions: Deletion of IL-1B is protective for AAA development in a murine elastase model and appears to be a critical step in the pathway for AAA formation. IL-1B deletion appears to inhibit the inflammatory pathway through decreased macrophage and neutrophil mural infiltration and decreased MMP2, 3, and 9 expression. Furthermore, IL-1B deletion is associated with preservation of elastin fibers and inhibition of smooth muscle cell phenotypic switching. IL-1B seems to play a central role in AAA formation and may illustrate future pharmacologic targets for AAA prevention.
- © 2012 by American Heart Association, Inc.