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Objective-In this article, we studied the effect of acetyl-11-keto-␤-boswellic acid (AK␤BA), a natural inhibitor of the proinflammatory transcription factor NF-B on the development of atherosclerotic lesions in apolipoprotein E-deficient (apoE Ϫ/Ϫ ) mice. Methods and Results-Atherosclerotic lesions were induced by weekly LPS injection in apoE Ϫ/Ϫ mice. LPS alone increased atherosclerotic lesion size by Ϸ100%, and treatment with AK␤BA significantly reduced it by Ϸ50%. Moreover, the activity of NF-B was also reduced in the atherosclerotic plaques of LPS-injected apoE Ϫ/Ϫ mice treated with AK␤BA. As a consequence, AK␤BA treatment led to a significant downregulation of several NF-B-dependent genes such as MCP-1, MCP-3, IL-1␣, MIP-2, VEGF, and TF. By contrast, AK␤BA did not affect the plasma concentrations of triglycerides, total cholesterol, antioxidized LDL antibodies, and various subsets of lymphocytederived cytokines. Moreover, AK␤BA potently inhibited the IB kinase (IKK) activity immunoprecipitated from LPS-stimulated mouse macrophages and mononuclear cells leading to decreased phosphorylation of IB␣ and inhibition of p65/NF-B activation. Comparable AK␤BA-mediated inhibition was also observed in LPS-stimulated human macrophages. Conclusion-The

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