Simvastatin Treatment Upregulates Anti-Fibrotic Bone Morphogenetic Protein-7 Expression at Rat Cardiac Allograft Rejection

Pharmacology. 2016;98(5-6):204-208. doi: 10.1159/000447305. Epub 2016 Jul 1.

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.

Conclusion: The beneficial effect of statin treatment on cardiac allograft may in part be mediated through the upregulation of BMP-7.

MeSH terms

  • Allografts / drug effects*
  • Allografts / metabolism
  • Animals
  • Bone Morphogenetic Protein 7 / biosynthesis*
  • Gene Expression Regulation
  • Graft Rejection / metabolism
  • Graft Rejection / prevention & control*
  • Heart Transplantation / adverse effects*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Male
  • Rats
  • Rats, Wistar
  • Simvastatin / pharmacology*
  • Simvastatin / therapeutic use
  • Up-Regulation / drug effects*
  • Up-Regulation / physiology

Substances

  • Bone Morphogenetic Protein 7
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Simvastatin