title: MnTBAP increases BMPR-II expression in endothelial cells and attenuates vascular inflammation.
abstract: The endothelium plays an important role during vascular inflammation. 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. Manganese (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) has been shown to mimic some of the effects of MnSOD and prevented the development of diabetes and obesity. However, its effect on vascular inflammation and the underlying mechanism is still unknown.
  
  
  
  Leukocyte adhesion was evaluated in-vivo and in-vitro using dynamic flow chamber and intravital microscopy in mice. Expression of adhesion molecules induced by TNFα and adhesion of leukocytes to the vessel wall were inhibited by MnTBAP. The anti-inflammatory effect of MnTBAP was partly mediated by up-regulation of the BMPR-II and Smad dependent pathway. Additionally, MnTBAP decelerated the turn-over of endogenous BMPR-II.
  
  
  
  Our data demonstrate that MnTBAP activates Smad signaling, preserves the turn-over of BMPR-II and elicits anti-inflammatory effects in endothelial cells, partly mediated by BMPR-II. This finding suggests a potential therapeutic impact of MnTBAP in the treatment of vascular inflammation.
authors.affiliation: Department of Cardiology and Angiology I, Heart Center, Medical Faculty, University of Freiburg, Freiburg, Germany.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Cardiology and Angiology I, Heart Center, Medical Faculty, University of Freiburg, Freiburg, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Einert
authors.affiliation: Department of Cardiology and Angiology I, Heart Center, Medical Faculty, University of Freiburg, Freiburg, Germany.
authors.forename: Hannah
authors.initials: H
authors.lastname: Schmitt
authors.affiliation: Department of Cardiology and Angiology I, Heart Center, Medical Faculty, University of Freiburg, Freiburg, Germany.
authors.forename: Zhengguan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiology and Angiology I, Heart Center, Medical Faculty, University of Freiburg, Freiburg, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Pankratz
authors.affiliation: Department of Cardiology and Angiology I, Heart Center, Medical Faculty, University of Freiburg, Freiburg, Germany.
authors.forename: Christoph B
authors.initials: CB
authors.lastname: Olivier
authors.affiliation: Department of Cardiology and Angiology I, Heart Center, Medical Faculty, University of Freiburg, Freiburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.affiliation: 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
authors.affiliation: Department of Cardiology and Angiology I, Heart Center, Medical Faculty, University of Freiburg, Freiburg, Germany. Electronic address: martin.moser@universitaets-herzzentrum.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Moser
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics; D002448:Cell Adhesion; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014652:Vascular Diseases / Q000473:pathology*
chemical_list: D000893:Anti-Inflammatory Agents; D008665:Metalloporphyrins; D051785:Smad Proteins; D014409:Tumor Necrosis Factor-alpha; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D013482:Superoxide Dismutase; D052006:Bone Morphogenetic Protein Receptors, Type II
keywords: BMPR-II; Endothelial cell; Inflammation; MnTBAP