Activation of the NF-kappa B and I kappa B system in smooth muscle cells after rat arterial injury. Induction of vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1.

The NF-kappa B transcription factor family and its inhibitory proteins (I kappa B) form an autoregulatory system that has been linked to endothelial gene expression and vascular disease. To determine the role of the NF-kappa B/I kappa B system in smooth muscle cells (SMCs) in vivo, the present study used the balloon catheter injury model in the rat carotid artery. The NF-kappa B family members p50, p65, p52, c-Rel, and RelB as well as the inhibitor proteins I kappa B alpha, I kappa B beta, and p105 were present in uninjured arteries as determined by immunoblotting. Using electromobility shift assays, low levels of constitutively activated p50, p65, and c-Rel were seen in normal carotid arteries and a fivefold induction occurred during times of rapid SMC proliferation and neointima formation after balloon denudation. Furthermore, immediately after injury, the levels of I kappa B alpha, I kappa B beta, and p105 were dramatically reduced. Expression of the NF-kappa B-regulated genes, vascular cell adhesion molecule (VCAM)-1 and monocyte chemotactic protein (MCP)-1, was apparent in SMCs within 4 hours after injury. Macrophage infiltration occurred in parallel with the expression of VCAM-1 and MCP-1, and these inflammatory cells were present on the luminal surface of injured vessels during intimal lesion formation. In chronically denuded vessels, the SMCs on the luminal surface continued to express high levels of VCAM-1 and MCP-1, which may account for the increased presence of macrophages. Together, these findings link the activation of NF-kappa B to intimal lesion formation and to the inflammatory response associated with SMCs after vascular injury.