Int6/eIF3e Silencing Promotes Placenta Angiogenesis in a Rat Model of Pre-eclampsia

Sci Rep. 2018 Jun 12;8(1):8944. doi: 10.1038/s41598-018-27296-2.

Abstract

We investigated whether stable eukaryotic translation initiation factor 3e/inter 6 (eIF-3e/Int6) RNA-silencing (siRNA-Int6) can ameliorate pre-eclampsia (PE) by promoting angiogenesis in an N-nitro-L-arginine methyl ester (L-NAME)-induced rat pre-eclampsia (PE) model. Twenty-four pregnant female Sprague-Dawley rats were allocated into 4 groups, including controls (Con) without any treatment, and 18 from gestational day (GD) 7 to GD17 L-NAME-treated rats, which were divided into stable siRNA-Int6 transfected (siRNA-Int6), negative vector control siRNA (NC-siRNA) and PE control (PE-Con) groups. All adenovirus siRNA transfections were performed on GD7 via intravenous tail injection. On GD0, GD11 and GD17, blood pressure, and on GD6 and GD17, protein estimations in 24 h urine samples were conducted. All animals were sacrificed on GD18. In the PE-Con group, placental Int6 was expressed to a significantly greater level than in the Con group, which was reversed by the application of siRNA-Int6. Blood pressure and proteinuria were significantly lower in the siRNA-Int6 group than in the PRE-Con group. As shown by CD31 and IB4 expression, placental micro-vascular density (MVD) was significantly higher in the siRNA-Int6 group than in the PE-Con and NC-siRNA groups, which has accompanied by enhanced trophoblast invasion. Int6 silencing alleviated the maternal clinical manifestations of pre-eclampsia and promoted placental angiogenesis in pregnant L-NAME-treated rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure / genetics
  • Blood Pressure / physiology
  • Disease Models, Animal
  • Eukaryotic Initiation Factor-3 / genetics*
  • Eukaryotic Initiation Factor-3 / metabolism
  • Female
  • Humans
  • NG-Nitroarginine Methyl Ester
  • Neovascularization, Physiologic / genetics*
  • Neovascularization, Physiologic / physiology
  • Placenta / blood supply*
  • Placenta / metabolism
  • Pre-Eclampsia / chemically induced
  • Pre-Eclampsia / genetics*
  • Pre-Eclampsia / metabolism
  • Pregnancy
  • Proteinuria / genetics
  • Proteinuria / metabolism
  • RNA Interference*
  • Rats, Sprague-Dawley

Substances

  • Eukaryotic Initiation Factor-3
  • NG-Nitroarginine Methyl Ester