Abstract 13775: Increased Atherosclerosis in the Lack of IkBNS in LDL Receptor-deficient Mice is Associated With Increased Interleukin-6 Production by Macrophages

Background: IκBNS is a nuclear IκB protein which regulates nuclear factor-κB dependent interleukin (IL) -6 production. Although IL-6 is an important biomarker for cardiovascular diseases, the role of IκBNS in the development of atherosclerosis is poorly understood. Methods and Results: Mice that lacked IκBNS (IκBNS-/-) were crossed with LDL receptor-deficient (LDLr-/-) mice and formation of atherosclerotic lesion was analyzed after 16 weeks consumption of a high-fat diet. When compared with single LDLr-/- mice (n=6), the surface atherosclerotic lesions in aortas were significantly increased in IκBNS-/-LDLr-/- mice (n=6) (22.7 ± 3.0% vs. 6.2 ± 1.4 %; p <0.001)(Figure). Immunostaining revealed significant increase in both Mac-3-positive (1.6-fold, p <0.05) and α-SMA-positive (3.6-fold, p <0.01) lesions in IκBNS-/-LDLr-/- mice compared with LDLr-/- mice. Furthermore, IL-6 expression (2.2-fold, p<0.001), and percent phospho-STAT3-positive cell (1.9-fold, p<0.05) were increased in IκBNS-/-LDLr-/- mice, indicat...