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Accession Number:
AD1044372
Title:
Characterizing Myeloid Cell Activation in NF1 Vasculopathy
Report Date:
2017-07-01
Abstract:
The overarching theme of our NF1YI proposal is to gain mechanistic insight and develop therapeutic targets for the prevention/treatment 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.
Document Type:
Conference:
Journal:
Pages:
45
File Size:
12.51MB
W81XWH-15-1-0228
(W81XWH1510228);
Contracts:
Grants:
Distribution Statement:
Approved For Public Release
