title: E-Selectin Inhibition Mitigates Splenic HSC Activation and Myelopoiesis in Hypercholesterolemic Mice With Myocardial Infarction.
abstract: Atherosclerosis is a chronic disease characterized by lipid accumulation in the arterial wall. After myocardial infarction (MI), atherosclerotic plaques are infiltrated by inflammatory myeloid cells that aggravate the disease and increase the risk of secondary myocardial ischemia. Splenic myelopoiesis provides a steady flow of myeloid cells to inflamed atherosclerotic lesions after MI. Therefore, targeting myeloid cell production in the spleen could ameliorate increased atherosclerotic plaque inflammation after MI.
  
  
  
  Here we show that MI increases splenic myelopoiesis by driving hematopoietic stem and progenitor cells into the cell cycle. In an atherosclerotic mouse model, E-selectin inhibition decreased hematopoietic stem and progenitor cell proliferation in the spleen after MI. This led to reduced extramedullary myelopoiesis and decreased myeloid cell accumulation in atherosclerotic lesions. Finally, we observed stable atherosclerotic plaque features, including smaller plaque size, reduced necrotic core area, and thicker fibrous cap after E-selectin inhibition.
  
  
  
  Inhibiting E-selectin attenuated inflammation in atherosclerotic plaques, likely by reducing leukocyte recruitment into plaques and by mitigating hematopoietic stem and progenitor cell activation in the spleen of mice with MI.
authors.affiliation: From the Center for Systems Biology, Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston (P.D., F.F.H., Y.S., Y.I., B.T., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and GlycoMimetics Inc, Rockville, MD (J.L.M.).
authors.forename: Partha
authors.initials: P
authors.lastname: Dutta
authors.affiliation: From the Center for Systems Biology, Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston (P.D., F.F.H., Y.S., Y.I., B.T., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and GlycoMimetics Inc, Rockville, MD (J.L.M.).
authors.forename: Friedrich Felix
authors.initials: FF
authors.lastname: Hoyer
authors.affiliation: From the Center for Systems Biology, Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston (P.D., F.F.H., Y.S., Y.I., B.T., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and GlycoMimetics Inc, Rockville, MD (J.L.M.).
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: From the Center for Systems Biology, Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston (P.D., F.F.H., Y.S., Y.I., B.T., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and GlycoMimetics Inc, Rockville, MD (J.L.M.).
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Iwamoto
authors.affiliation: From the Center for Systems Biology, Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston (P.D., F.F.H., Y.S., Y.I., B.T., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and GlycoMimetics Inc, Rockville, MD (J.L.M.).
authors.forename: Benoit
authors.initials: B
authors.lastname: Tricot
authors.affiliation: From the Center for Systems Biology, Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston (P.D., F.F.H., Y.S., Y.I., B.T., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and GlycoMimetics Inc, Rockville, MD (J.L.M.).
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.affiliation: From the Center for Systems Biology, Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston (P.D., F.F.H., Y.S., Y.I., B.T., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and GlycoMimetics Inc, Rockville, MD (J.L.M.).
authors.forename: John L
authors.initials: JL
authors.lastname: Magnani
authors.affiliation: From the Center for Systems Biology, Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston (P.D., F.F.H., Y.S., Y.I., B.T., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and GlycoMimetics Inc, Rockville, MD (J.L.M.).
authors.forename: Filip K
authors.initials: FK
authors.lastname: Swirski
authors.affiliation: From the Center for Systems Biology, Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston (P.D., F.F.H., Y.S., Y.I., B.T., R.W., F.K.S., M.N.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); and GlycoMimetics Inc, Rockville, MD (J.L.M.). mnahrendorf@mgh.harvard.edu.
authors.forename: Matthias
authors.initials: M
authors.lastname: Nahrendorf
mesh_terms: D000818:Animals; D001018:Aortic Diseases / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D019040:E-Selectin / Q000378:metabolism*; D005355:Fibrosis; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D006937:Hypercholesterolemia / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D038042:Myelopoiesis / Q000187:drug effects*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009336:Necrosis; D058226:Plaque, Atherosclerotic; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000187:drug effects* / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D019040:E-Selectin
keywords: E-selectin; HSC; atherosclerosis; myelopoiesis; myocardial infarction