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Here we define the contribution of myeloid subpopulations to NF1 arteriopathy. Neutrophils from WT and <jats:italic>Nf1<\/jats:italic>+\/\u2013 mice were functionally assessed in the presence of MEK and farnesylation inhibitors in vitro and neutrophil recruitment to lipopolysaccharide was assessed in WT and <jats:italic>Nf1<\/jats:italic>+\/\u2013 mice. Littermate 12\u201315\u00a0week-old male wildtype and <jats:italic>Nf1<\/jats:italic>+\/\u2013 mice were subjected to carotid artery ligation and provided either a neutrophil depleting antibody (1A8), liposomal clodronate to deplete monocytes\/macrophages, or PD0325901 and neointima size was assessed 28\u00a0days after injury. Bone marrow transplant experiments assessed monocyte\/macrophage mobilization during neointima formation. <jats:italic>Nf1<\/jats:italic>+\/\u2013 neutrophils exhibit enhanced proliferation, migration, and adhesion via p21<jats:sup>Ras<\/jats:sup> activation of MEK in vitro and in vivo. Neutrophil depletion suppresses circulating Ly6C<jats:sup>low<\/jats:sup> monocytes and enhances neointima size, while monocyte\/macrophage depletion and deletion of <jats:italic>CCR2<\/jats:italic> in bone marrow cells abolish neointima formation in <jats:italic>Nf1<\/jats:italic>+\/\u2013 mice. Taken together, these findings suggest that neurofibromin-MEK-ERK activation in circulating neutrophils and monocytes during arterial remodeling is nuanced and points to important cross-talk between these populations in the pathogenesis of NF1 arteriopathy.<\/jats:p>","DOI":"10.1038\/s41598-021-03750-6","type":"journal-article","created":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T11:03:53Z","timestamp":1640084633000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["MEK inhibition exerts temporal and myeloid cell-specific effects in the pathogenesis of neurofibromatosis type 1 arteriopathy"],"prefix":"10.1038","volume":"11","author":[{"given":"Rebekah","family":"Tritz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farlyn Z.","family":"Hudson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerie","family":"Harris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pushpankur","family":"Ghoshal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bhupesh","family":"Singla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiping","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabor","family":"Csanyi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian K.","family":"Stansfield","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,12,21]]},"reference":[{"key":"3750_CR1","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/nrc3911","volume":"15","author":"N Ratner","year":"2015","unstructured":"Ratner, N. & Miller, S. 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