Abstract 10910: Interleukin-1 Receptor Antagonist Derived from Both Bone Marrow and Non-Bone Marrow Cells Participates Importantly in Neointimal Formation After Injury
Background: Interleukin-1 receptor antagonist(IL-1Ra) is one of the most important anti-inflammatory cytokines. IL-1Ra is expressed on multiple cell types in neointimal formation such as bone marrow (BM)-derived cells and non-BM intrinsic arterial cells. However, the importance of various cell types as sources of IL-1Ra remains unknown.
Methods and Results: To determine the contribution of IL-1Ra-deficient (KO) and wild-type (WT) BM cells for neointimal formation, we developed 4 types of BM chimeric (BMTWT→WT (n=10), BMTKO→WT (n=12), BMTWT→KO (n=12), BMTKO→KO (n=10)) mice. At 4 weeks after BMT, vascular injury was performed by placing a nonocclusive cuff around the femoral artery. Intimal and medial areas were measured 2 weeks after injury. No significant differences in systolic arterial pressure srand plasma lipid levels were observed among 4 groups. The neointimal formation in BMTWT→KO mice was significantly reduced compared with BMTKO→KO mice (P<0.001), but significantly larger compare with BMTKO→WT (P<0.01) and BMTWT→WT mice (P<0.01). In contrast, the neointimal formation in BMTKO→WT mice was significantly increased compared with BMTWT→WT mice (P<0.05), but significantly smaller compare with BMTWT→KO (P<0.01) and BMTKO→KO mice (P<0.0001) (Figure A). Immunohistochemical analysis revealed that IL-1Ra localized the endothelium and smooth muscle cells in injured arteries of both BMTKO→WT and BMTWT→WT mice. Moreover, serum levels of IL-1Ra at 3 days after injury were significant lower in BMTWT→KO mice compared with BMTKO→WT (P<0.001) and BMTWT→WT mice (P<0.0001). As expected, the IL-1Ra protein was not detected in BMTKO→KO mice (Figure B).
Conclusions: These results demonstrate an essential role of IL-1Ra in BM-derived cells in the pathogenesis of neointima formation after injury. However, IL-1Ra in non-BM intrinsic arterial cells and secreted form of IL-1Ra must also play an important role in suppression of intimal hyperplasia after injury.
- © 2011 by American Heart Association, Inc.