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Nuclear factor kappa B (NF-kappa B) activation has been observed in human atherosclerotic plaques and is enhanced in unstable coronary plaques, but whether such activation has a protective or pathophysiological role remains to be determined. We addressed this question by developing a short-term culture system of cells isolated from human atherosclerotic tissue, allowing efficient gene transfer to directly investigate signaling pathways in human atherosclerosis. We found that NF-kappa B is activated in these cells and that this activity involves p65, p50, and c-Rel but not p52 or RelB. This NF-kappa B activation can be blocked by overexpression of I kappa B alpha or dominant-negative I kappa B kinase (IKK)-2 but not dominant-negative IKK-1 or NF-kappa B-inducing kinase, resulting in selective inhibition of inflammatory cytokines (tumor necrosis factor alpha, IL-6, and IL-8), tissue factor, and matrix metalloproteinases without affecting the antiinflammatory cytokine IL-10 or tissue inhibitor of matrix metalloproteinases. Our results demonstrate that the canonical pathway of NF-kappa B activation that involves p65, p50, c-Rel, and IKK-2 is activated in human atherosclerosis and results in selective up-regulation of major proinflammatory and prothrombotic mediators of the disease.

Original publication




Journal article


Proc natl acad sci u s a

Publication Date





5634 - 5639


Actins, Adenoviridae, Arteriosclerosis, CD3 Complex, CD40 Ligand, Cells, Cultured, Gene Transfer, Horizontal, Humans, I-kappa B Kinase, Inflammation, Interleukin-6, Interleukin-8, Matrix Metalloproteinase Inhibitors, Matrix Metalloproteinases, Myocytes, Smooth Muscle, NF-kappa B, NF-kappa B p50 Subunit, Protein-Serine-Threonine Kinases, Thromboplastin, Thrombosis, Tissue Inhibitor of Metalloproteinase-1, Transcription Factor RelA