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Stroke. 2004 Feb;35(2):458-63. Epub 2004 Jan 22.

NF-kappaB activation and Fas ligand overexpression in blood and plaques of patients with carotid atherosclerosis: potential implication in plaque instability.

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Vascular Research Laboratory, Fundación Jiménez Díaz, Autonoma University, Madrid, Spain.



Apoptosis is present in human atherosclerotic lesions. Nuclear factor-kappaB (NF-kappaB) is involved in the transcriptional regulation of the proapoptotic protein Fas ligand (FasL). We have analyzed NF-kappaB activation and FasL expression in atherosclerotic plaques and peripheral blood mononuclear cells (PBMCs) of patients with carotid stenosis.


NF-kappaB activation and FasL and active caspase-3 expression were analyzed in 32 human carotid plaques. NF-kappaB activation and FasL mRNA were tested in PBMCs of patients and healthy volunteers. We analyzed whether the NF-kappaB inhibitor parthenolide regulates FasL expression and cytotoxicity in human T cells.


The inflammatory region of plaques showed an increase in NF-kappaB activation (3393+/-281 versus 1029+/-100 positive nuclei per mm(2), P<0.001) and FasL (16+/-1.4% versus 13+/-1.8%, P<0.05) and active caspase-3 (3.3+/-0.6 versus 1.5+/-0.3%, P<0.05) expression compared with the fibrous area. Activated NF-kappaB and FasL protein were colocalized in plaque cells. In PBMCs obtained from those patients the day of endarterectomy, NF-kappaB activation and FasL expression were significantly increased compared with healthy controls (1.5+/-0.1 versus 0.5+/-0.1 and 2.1+/-0.1 versus 1.2+/-0.1 arbitrary units, respectively; P<0.001). There was a significant correlation between NF-kappaB activation and FasL expression. In activated T cells, parthenolide decreased NF-kappaB activation, FasL promoter activity, and mRNA expression. Parthenolide also decreased cytotoxicity of activated Jurkat cells on FasL-sensitive cells.


NF-kappaB activation and FasL overexpression occur in PBMCs and atherosclerotic lesions of patients with carotid stenosis. The NF-kappaB-FasL pathway could be involved in the mechanisms underlying plaque instability in humans.

[Indexed for MEDLINE]

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