Expression of NF-kappa B and I kappa B-alpha by aortic endothelium in an arterial injury model.

Endothelial cells at sites of inflammatory responses express a variety of genes that are under the control of nuclear factor NF-kappa B, a transcription factor that with its inhibitors may be linked in an autoregulatory system that can be activated by multiple signals relevant to vascular pathophysiology. A model of limited endothelial denudation in the aorta of rats and mice was used to study the role of NF-kappa B and the inhibitor I kappa B-alpha Using en face techniques for in situ hybridization and immunostaining, normal endothelium showed diffuse cytoplasmic immunoreactivity for the NF-kappa B components p50 and p65 as well as the inhibitor I kappa B-alpha Within 45 minutes after wounding, nuclear staining for both NF-kappa B components was noticeable in the endothelial cells at the wound edge, which was followed by a dramatic induction of VCAM-1 mRNA and protein 3 hours later. Leading edge endothelial cells also responded with up-regulated expression of both NF-kappa B components and I kappa B-alpha. The increased expression of p50, p65, VCAM-1, and I kappa B-alpha persisted in replicating endothelium that was associated with adhesion of monocyte/macrophages to these cells. Expression levels returned to normal after regeneration. Our data establish for the first time the presence of the NF-kappa B/I kappa B-alpha system in the vasculature and demonstrate a correlation between activation of the regulatory system and induction of a kappa B-dependent endothelial adhesion molecule in an animal model of arterial injury. This autoregulatory system may be an important homeostatic mechanism in the vessel wall.