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 end othelial gene expression and vascular disease. To determine the role o f the NF-kappa B/I kappa B system in smooth muscle cells (SMCs) in viv o, 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, a nd RelB as well as the inhibitor proteins I kappa B alpha, I kappa B b eta, and p105 were present in uninjured arteries as determined by immu noblotting. Using electromobility shift assays, low levels of constitu tively activated p50, p65, and c-Rel were seen in normal carotid arter ies and a fivefold induction occurred during times of rapid SMC prolif eration and neointima formation after balloon denudation. Furthermore, immediately after injury, the levels of I kappa B alpha, I kappa B be ta, and p105 were dramatically reduced. Expression of the NF-kappa B-r egulated 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 express ion 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 cont inued to express high levels of VCAM-1 and MCP-1, which may account fo r the increased presence of macrophages. Together, these findings link the activation of NF-kappa B to intimal lesion formation and to the i nflammatory response associated with SMCs after vascular injury.