Characterizing Myeloid Cell Activation in NF1 Vasculopathy
Abstract
The overarching theme of our NF YI proposal is to gain mechanistic insight and develop therapeutic targets for the prevention/treatment of neurofibromatosis type 1 (NF1) related cardiovascular disease. Previously, we developed mouse models of arterial stenosis and aneurysm formation that resemble disease in NF1 patients. We have completely interrogated the MCP1/CCR2 signaling pathway in the pathogenesis of NF1 arterial stenosis and a published manuscript is attached to this report. The primary findings of these studies were that CCR2 activation is required for the infiltration of neurofibromin-deficient myeloid cells, the primary cellular effectors of NF1 arterial stenosis, and that pharmacologic inhibition of CCR2 activation is a viable therapeutic option for the prevention and/or treatment of NF1 arterial stenosis. The second aim of our proposal was to interrogate reactive oxygen species production in the generation of NF1 aneurysms. We have initiated work on the proposed experiments using our NF1-related aneurysm model and have generated the mice and tissues for the proposed experiments. We have also begun experiments in a separate model system (calcium chloride) to support our previous findings of enhanced aneurysm formation in Nf1 heterozygous mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2016
- Accession Number
- AD1034006
Entities
People
- Brian K. Stansfield
Organizations
- Augusta University