title: MnTBAP stimulates angiogenic functions in endothelial cells through mitofusin-1.
abstract: OBJECTIVE
  Angiogenesis is defined as the sprouting of capillaries from pre-existing vasculature. It is a complex process that includes endothelial proliferation, migration, and tube formation. Previous data have demonstrated a high expression level of manganese-superoxide dismutase (MnSOD) in endothelial cells and suggested an important role of MnSOD in several cardiovascular diseases. In addition, manganese (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) has been shown to mimic some of the effects of MnSOD in various tissues. However, its effect on the vasculature remains unknown.
  
  
  RESULTS
  HUVECs were treated with MnTBAP. Migration, tube formation, and capillary sprouting assays were performed to evaluate the pro-angiogenic effect in vitro. Matrigel plug assay was performed to assess capillary ingrowth in vivo. Compared to control, treatment with MnTBAP revealed increased cell migration, tube formation and capillary sprouting along with more capillary ingrowth in the Matrigel plug assay. This effect was mediated through a mitofusin (Mfn)-1-dependent pathway. Expression of Tie-2, Ang-2 and VEGF mRNA was increased in muscle tissues after ligation in MnTBAP treated mice. However, revascularization in the hindlimb ischemia model was not statistically significant at day 10 in MnTBAP treated mice.
  
  
  CONCLUSIONS
  In summary, our data demonstrate a strong pro-angiogenic, but less pro-arteriogenic effect of MnTBAP in HUVECs mediated by Mfn-1.
authors.affiliation: Vascular Medicine Research Unit, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Freiburg, Germany.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Vascular Medicine Research Unit, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg, Saar, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Gensch
authors.affiliation: Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Freiburg, Germany.
authors.forename: Constanze
authors.initials: C
authors.lastname: Keller
authors.affiliation: Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Freiburg, Germany.
authors.forename: Hannah
authors.initials: H
authors.lastname: Schmitt
authors.affiliation: Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Freiburg, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Esser
authors.affiliation: Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Freiburg, Germany. Electronic address: martin.moser@universitaets-herzzentrum.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Moser
authors.affiliation: Vascular Medicine Research Unit, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Section of Cardiology, University of Chicago Medical Center, Chicago, IL, USA. Electronic address: jliao@medicine.bsd.uchicago.edu.
authors.forename: James K
authors.initials: JK
authors.lastname: Liao
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D042783:Endothelial Cells / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008665:Metalloporphyrins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D004338:Drug Combinations; D007797:Laminin; D008665:Metalloporphyrins; D033681:Mitochondrial Membrane Transport Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D033921:Vesicular Transport Proteins; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; C059485:matrigel; D003094:Collagen; D042787:Receptor, TIE-2; D020558:GTP Phosphohydrolases
keywords: Angiogenesis; Endothelial cell; MnTBAP