Separately, chimeric Nf1+/- were generated with specific deletion of CCR2 in bone marrow cells or vascular wall cells and carotid artery ligation was performed. Nf1+/- mice with genetic deletion of MCP-1 or CCR2 were subjected to arterial injury Control and ligated arteries were analyzed for neointima formation. The left common carotid artery was ligated proximal to the bifurcation and mice were allowed to recover for 28 days.

Methods Used: We utilized a carotid artery ligation model to induce neointima formation. Therefore, we tested the hypothesis that activation of the MCP-1/CCR2 signaling cascade mediates the recruitment of neurofibromin-deficient myeloid cells to induce arterial stenosis. We recently showed that loss of a single Nf1 gene copy in myeloid cells is sufficient to induce arterial stenosis after arterial injury and enhance the mobilization of pro-inflammatory Ly6Chi CCR2+ monocytes. Some NF1 patients develop arterial stenosis in adolescence and early adulthood. Loss of neurofibromin, as observed in persons with neurofibromatosis type 1 (NF1), sensitizes cells to growth factor stimulation and aberrant Ras activation. Purpose of Study: Neurofibromin results from mutations in the NF1 gene and functions as a negative regulator of Ras activity.

1Georgia Regents University, Augusta, GA and 2Indiana University, Indianapolis, IN. 1 NEUROFIBROMIN REGULATES MONOCYTE/MACROPHAGE FUNCTION

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