Overexpression of farnesyl pyrophosphate synthase increases myocardial ischemia/reperfusion injury in mice

Gene. 2018 Sep 25:672:72-78. doi: 10.1016/j.gene.2018.05.116. Epub 2018 Jun 1.

Abstract

Farnesyl pyrophosphate synthase (FPPS) is a vital enzyme in the mevalonate pathway. Our previous study has indicated that overexpression of FPPS increases hypoxia/reoxygenation (HR) injury in Heart-derived H9c2 Cells. Hence, we designed this experiment to further investigate the effect of FPPS on myocardial ischemia/reperfusion (MIR) injury using a transgenic (Tg) model, and explore the relevant mechanisms. The results showed that when mouse hearts were subjected to ex vivo I/R, Tg mice have a higher CK and LDH, a larger myocardial infarct size and lower heart function recovery. These phenomena are associated with the increased Rac1 activity and ROS generation. These findings point to that FPPS might be a potential target in preventing MIR in vivo.

Keywords: Langendorff; Rac1; Reactive oxygen species.

MeSH terms

  • Animals
  • Female
  • Gene Expression
  • Geranyltranstransferase / genetics*
  • Geranyltranstransferase / metabolism
  • Male
  • Mice, Transgenic
  • Myocardial Infarction / enzymology
  • Myocardial Infarction / pathology
  • Myocardial Reperfusion Injury / enzymology*
  • Myocardial Reperfusion Injury / pathology
  • Myocardium / enzymology
  • Myocardium / pathology
  • Neuropeptides / metabolism
  • Reactive Oxygen Species / metabolism
  • rac1 GTP-Binding Protein / metabolism

Substances

  • Neuropeptides
  • Rac1 protein, mouse
  • Reactive Oxygen Species
  • Geranyltranstransferase
  • rac1 GTP-Binding Protein