title: CD45 Expression in Mitral Valve Endothelial Cells After Myocardial Infarction.
abstract: BACKGROUND
  Ischemic mitral regurgitation, a complication after myocardial infarction (MI), induces adaptive mitral valve (MV) responses that may be initially beneficial but eventually lead to leaflet fibrosis and MV dysfunction. We sought to examine the MV endothelial response and its potential contribution to ischemic mitral regurgitation.
  
  
  OBJECTIVE
  Endothelial, interstitial, and hematopoietic cells in MVs from post-MI sheep were quantified. MV endothelial CD45, found post MI, was analyzed in vitro.
  
  
  RESULTS
  Ovine MVs, harvested 6 months after inferior MI, showed CD45, a protein tyrosine phosphatase, colocalized with von Willebrand factor, an endothelial marker. Flow cytometry of MV cells revealed significant increases in CD45+endothelial cells (VE-cadherin+/CD45+/α-smooth muscle actin [SMA]+and VE-cadherin+/CD45+/αSMA- cells) and possible fibrocytes (VE-cadherin-/CD45+/αSMA+) in inferior MI compared with sham-operated and normal sheep. CD45+cells correlated with MV fibrosis and mitral regurgitation severity. VE-cadherin+/CD45+/αSMA+cells suggested that CD45 may be linked to endothelial-to-mesenchymal transition (EndMT). MV endothelial cells treated with transforming growth factor-β1 to induce EndMT expressed CD45 and fibrosis markers collagen 1 and 3 and transforming growth factor-β1 to 3, not observed in transforming growth factor-β1-treated arterial endothelial cells. A CD45 protein tyrosine phosphatase inhibitor blocked induction of EndMT and fibrosis markers and inhibited EndMT-associated migration of MV endothelial cells.
  
  
  CONCLUSIONS
  MV endothelial cells express CD45, both in vivo post MI and in vitro in response to transforming growth factor-β1. A CD45 phosphatase inhibitor blocked hallmarks of EndMT in MV endothelial cells. These results point to a novel, functional requirement for CD45 phosphatase activity in EndMT. The contribution of CD45+endothelial cells to MV adaptation and fibrosis post MI warrants investigation.
authors.affiliation: From the Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Harvard Medical School, MA (J.B., G.C., J.W.-S.); Cardiac Ultrasound Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston (D.-H.K., P.E.B., J.L.G., J.P.D.-B., J.B., M.L.G., S.M.S., M.M.S., B.A.M., R.A.L.); Division of Cardiology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea (D.-H.K.); and Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (J.K., W.S.I., E.A.). joyce.bischoff@childrens.harvard.edu.
authors.forename: Joyce
authors.initials: J
authors.lastname: Bischoff
authors.affiliation: From the Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Harvard Medical School, MA (J.B., G.C., J.W.-S.); Cardiac Ultrasound Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston (D.-H.K., P.E.B., J.L.G., J.P.D.-B., J.B., M.L.G., S.M.S., M.M.S., B.A.M., R.A.L.); Division of Cardiology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea (D.-H.K.); and Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (J.K., W.S.I., E.A.).
authors.forename: Guillem
authors.initials: G
authors.lastname: Casanovas
authors.affiliation: From the Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Harvard Medical School, MA (J.B., G.C., J.W.-S.); Cardiac Ultrasound Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston (D.-H.K., P.E.B., J.L.G., J.P.D.-B., J.B., M.L.G., S.M.S., M.M.S., B.A.M., R.A.L.); Division of Cardiology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea (D.-H.K.); and Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (J.K., W.S.I., E.A.).
authors.forename: Jill
authors.initials: J
authors.lastname: Wylie-Sears
authors.forename: Dae-Hee
authors.initials: DH
authors.lastname: Kim
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Bartko
authors.forename: J Luis
authors.initials: JL
authors.lastname: Guerrero
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Dal-Bianco
authors.forename: Jonathan
authors.initials: J
authors.lastname: Beaudoin
authors.forename: Michael L
authors.initials: ML
authors.lastname: Garcia
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Sullivan
authors.forename: Margo M
authors.initials: MM
authors.lastname: Seybolt
authors.forename: Brittan A
authors.initials: BA
authors.lastname: Morris
authors.forename: Joshua
authors.initials: J
authors.lastname: Keegan
authors.forename: Whitney S
authors.initials: WS
authors.lastname: Irvin
authors.forename: Elena
authors.initials: E
authors.lastname: Aikawa
authors.forename: Robert A
authors.initials: RA
authors.lastname: Levine
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D017493:Leukocyte Common Antigens / Q000096:biosynthesis* / Q000235:genetics; D008943:Mitral Valve / Q000166:cytology* / Q000378:metabolism*; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism*; D012756:Sheep
chemical_list: D017493:Leukocyte Common Antigens
keywords: endothelial cell; endothelial cell differentiation; flow cytometry; mitral valve; myocardial infarction