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Characterizing Myeloid Cell Activation in NF1 Vasculopathy

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[Technical Report, Annual Report]

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Georgia Regents Research Institute Inc.

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The overarching theme of our NF1YI proposal is to gain mechanistic insight and develop therapeutic targets for the preventiontreatment of neurofibromatosis type 1 NF1 related cardiovascular diseases. Cardiovascular disease affects upwards of 10 of the more than 2,000,000 persons with NF1 worldwide and presents with lesions in the proximal arteries such as arterial stenosis and aneurysm formation. We have developed murine models that closely resemble NF1 arterial stenosis and aneurysm formation, which are both primarily mediated through the infiltration of bone marrow derived myeloid cells into the vascular wall in Nf1 heterozygous mice. However, the pathological consequences of these cells are somewhat opposed, wherein arterial stenosis is the result of smooth muscle cell proliferation and inward remodeling and aneurysms are the result of smooth muscle cell apoptosis and outward remodeling. To better understand how neurofibromin-deficient myeloid cells can lead to different pathological outcomes, we propose to interrogate the recruitment of macrophages via monocyte chemotactic peptide-1 MCP-1 stimulation of its receptor CCR2 and the generation of reactive oxygen species, which are generated in excessive quantities by neurofibromin-deficient macrophages in our arterial stenosis and aneurysm models, respectively.


Subject Categories:

  • Medicine and Medical Research

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[A, Approved For Public Release]