The NF-kappaB and IkappaB system in injured arteries.

Activation of endothelial cells and dedifferentiation of smooth muscle cells (SMC) are events in the development of vascular disease. The NF-kappaB transcription factor family and its inhibitory proteins (IkappaB) have been implicated in regulating the expression of genes associated with the concomitant inflammatory response. To determine the role of the NF-kappaB/IkappaB system in vivo, the present study used the balloon catheter injury model in the rat carotid artery. Immunoblotting revealed that higher levels of the NF-kappaB family members p50, p52, p65, c-Rel, and RelB were expressed in injured arteries during lesion formation compared to normal vessels. Using electromobility shift assays, low levels of constitutively activated NF-kappaB were seen in normal carotid arteries and an induction occurred during times of rapid SMC proliferation. Furthermore, immediately after injury, the levels of the inhibitor proteins IkappaB alpha, IkappaB beta, and p105 were dramatically reduced. Consistent with the activation of NF-kappaB, vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemotactic protein-1 (MCP-1) were induced in SMC and endothelial cells as early as 4 h after injury and this was accompanied by adhesion of monocytes/macrophages. SMC forming a pseudoendothelium in chronically denuded vessels continued to express high levels of VCAM-1 and MCP-1, thus perpetuating the inflammatory response. These findings link the activation of NF-kappaB to the inflammatory response and to intimal lesion formation following vascular injury.