title: Simvastatin Treatment Upregulates Anti-Fibrotic Bone Morphogenetic Protein-7 Expression at Rat Cardiac Allograft Rejection.
abstract: BACKGROUND
  Bone morphogenetic protein (BMP)-7 mediates ischemic tolerance and anti-fibrotic effects in various organs such as kidney and heart. Recently, reno- and podocyte-protective effects of a potent HMG-CoA reductase inhibitor, pitavastatin, were accompanied by BMP-7 upregulation.
  
  
  METHODS
  Here, we investigated the effect of simvastatin treatment on BMP-7 expression in major MHC-mismatched rat cardiac allografts subjected to ischemia-reperfusion injury and adaptive immune activation at 10 days.
  
  
  RESULTS
  We localized Smad2 activity and Reca-1+ fibroblast specific protein-1+ immunoreactivity, suggesting endothelial-to-mesenchymal transition, at fibrotic borderline of cardiac allografts at 10 days. Simvastatin donor and recipient combination treatment significantly upregulated cardiac allograft BMP-7 expression when compared to nontreated controls at 10 days.
  
  
  CONCLUSIONS
  The beneficial effect of statin treatment on cardiac allograft may in part be mediated through the upregulation of BMP-7.
authors.affiliation: Transplantation Laboratory, University of Helsinki, Helsinki, Finland.
authors.forename: Emil J
authors.initials: EJ
authors.lastname: Holmström
authors.forename: Karl B
authors.initials: KB
authors.lastname: Lemström
authors.forename: Raimo
authors.initials: R
authors.lastname: Tuuminen
mesh_terms: D064591:Allografts / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000378:metabolism / Q000517:prevention & control*; D016027:Heart Transplantation / Q000009:adverse effects*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
chemical_list: D055419:Bone Morphogenetic Protein 7; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin