title: High-density lipoproteins reduce endothelial-to-mesenchymal transition.
abstract: OBJECTIVE
  Endothelial-to-mesenchymal transition is an inflammation-induced process by which endothelial cells can transdifferentiate into fibroblasts. Based on the endothelial-protective and antifibrotic effects of high-density lipoproteins (HDL), we aimed to investigate whether HDL can reduce endothelial-to-mesenchymal transition.
  
  
  RESULTS
  Therefore, human aortic endothelial cells were stimulated with the profibrotic factor transforming growth factor (TGF)-β1 in the presence or absence of HDL. Their impact on the transition of endothelial cells to mesenchymal-like cells was analyzed. Phase contrast microscopy demonstrated that HDL abrogated the TGF-β1-induced spindle-shape morphology in human aortic endothelial cells. Furthermore, HDL decreased the TGF-β1-mediated induction of α-smooth muscle actin expression and concomitant loss in endothelial cadherin expression, as shown by immunofluorescence staining and flow cytometry. In addition, HDL decreased the TGF-β1-induced collagen deposition in human aortic endothelial cells involving the scavenger receptor class B, type 1 and downstream phosphatidyl inositol-3-kinase following the findings that the HDL-mediated reduction was abrogated by scavenger receptor class B, type 1 siRNA knockdown and phosphatidyl inositol-3-kinase inhibition, respectively. The HDL-mediated reduction in endothelial-to-mesenchymal transition was associated with an induction of the inhibitory Smad, Smad 7.
  
  
  CONCLUSIONS
  We provide the first in vitro evidence that the endothelial-protective and antifibrotic effects of HDL include the reduction in endothelial-to-mesenchymal transition.
authors.affiliation: From the Department of Cardiology (F.S., B.P., C.T.) and Berlin-Brandenburg Center for Regenerative Therapy (BCRT) (K.M., C.T., S.V.L.), Charité-University-Medicine Berlin, Campus Virchow Klinikum (CVK), Berlin, Germany; Department of Cardiology, Deutsches Herzzentrum Berlin (DHZB), Berlin, Germany (B.P.); and Deutsches Zentrum für Herz Kreislaufforschung (DZHK), Standort Berlin/Charité, Germany (B.P., C.T., S.V.L.).
authors.forename: Frank
authors.initials: F
authors.lastname: Spillmann
authors.affiliation: From the Department of Cardiology (F.S., B.P., C.T.) and Berlin-Brandenburg Center for Regenerative Therapy (BCRT) (K.M., C.T., S.V.L.), Charité-University-Medicine Berlin, Campus Virchow Klinikum (CVK), Berlin, Germany; Department of Cardiology, Deutsches Herzzentrum Berlin (DHZB), Berlin, Germany (B.P.); and Deutsches Zentrum für Herz Kreislaufforschung (DZHK), Standort Berlin/Charité, Germany (B.P., C.T., S.V.L.).
authors.forename: Kapka
authors.initials: K
authors.lastname: Miteva
authors.affiliation: From the Department of Cardiology (F.S., B.P., C.T.) and Berlin-Brandenburg Center for Regenerative Therapy (BCRT) (K.M., C.T., S.V.L.), Charité-University-Medicine Berlin, Campus Virchow Klinikum (CVK), Berlin, Germany; Department of Cardiology, Deutsches Herzzentrum Berlin (DHZB), Berlin, Germany (B.P.); and Deutsches Zentrum für Herz Kreislaufforschung (DZHK), Standort Berlin/Charité, Germany (B.P., C.T., S.V.L.).
authors.forename: Burkert
authors.initials: B
authors.lastname: Pieske
authors.affiliation: From the Department of Cardiology (F.S., B.P., C.T.) and Berlin-Brandenburg Center for Regenerative Therapy (BCRT) (K.M., C.T., S.V.L.), Charité-University-Medicine Berlin, Campus Virchow Klinikum (CVK), Berlin, Germany; Department of Cardiology, Deutsches Herzzentrum Berlin (DHZB), Berlin, Germany (B.P.); and Deutsches Zentrum für Herz Kreislaufforschung (DZHK), Standort Berlin/Charité, Germany (B.P., C.T., S.V.L.).
authors.forename: Carsten
authors.initials: C
authors.lastname: Tschöpe
authors.affiliation: From the Department of Cardiology (F.S., B.P., C.T.) and Berlin-Brandenburg Center for Regenerative Therapy (BCRT) (K.M., C.T., S.V.L.), Charité-University-Medicine Berlin, Campus Virchow Klinikum (CVK), Berlin, Germany; Department of Cardiology, Deutsches Herzzentrum Berlin (DHZB), Berlin, Germany (B.P.); and Deutsches Zentrum für Herz Kreislaufforschung (DZHK), Standort Berlin/Charité, Germany (B.P., C.T., S.V.L.). sophie.van-linthout@charite.de.
authors.forename: Sophie
authors.initials: S
authors.lastname: Van Linthout
mesh_terms: D000199:Actins / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005355:Fibrosis; D006801:Humans; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D010641:Phenotype; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D034622:RNA Interference; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D000099152:Cadherin 5
chemical_list: D000199:Actins; D015703:Antigens, CD; D015820:Cadherins; D003094:Collagen; D008075:Lipoproteins, HDL; D058539:Phosphatidylinositol 3-Kinase; D051122:Scavenger Receptors, Class B; D053773:Transforming Growth Factor beta1; D000099152:Cadherin 5; C541116:ACTA2 protein, human; C495124:SCARB1 protein, human
keywords: HDL; aortic endothelial cells; endothelial-to-mesenchymal transition; fibrosis; transforming growth factor