Erythropoietin Mimetic Peptide (pHBSP) Corrects Endothelial Dysfunction in a Rat Model of Preeclampsia

Int J Mol Sci. 2020 Sep 15;21(18):6759. doi: 10.3390/ijms21186759.

Abstract

Preeclampsia is a severe disease of late pregnancy. Etiological factors and a pathogenetic pattern of events still require significant clarification, but it is now recognized that a large role is played by placentation disorders and emerging endothelial dysfunction. The administration of short-chain peptides mimicking the spatial structure of the B erythropoietin chain may become one of the directions of searching for new drugs for preeclampsia prevention and therapy. Simulation of ADMA-like preeclampsia in Wistar rats was performed by the administration of a non-selective NOS blocker L-NAME from the 14th to 20th day of pregnancy. The administration of the pHBSP at the doses of 10 µg/kg and 250 µg/kg corrected the established morphofunctional disorders. The greatest effect was observed at a dose of 250 µg/kg. There was a decrease in systolic and diastolic blood pressure by 31.2 and 32.8%, respectively (p < 0.0001), a decrease in the coefficient of endothelial dysfunction by 48.6% (p = 0.0006), placental microcirculation increased by 82.8% (p < 0.0001), the NOx concentration was increased by 42,6% (p = 0.0003), the greater omentum edema decreased by 11.7% (p = 0.0005) and proteinuria decreased by 76.1% (p < 0.0002). In addition, there was an improvement in the morphological pattern of the fetoplacental complex and the ratio of BAX to Bcl-2 expression which characterizes the apoptotic orientation of the cells.

Keywords: Wistar rats; endothelial dysfunction; erythropoietin-derived peptide; pHBSP; placenta; preeclampsia.

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Disease Models, Animal
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Erythropoietin / metabolism*
  • Female
  • Microcirculation / drug effects
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Oligopeptides / pharmacology*
  • Placenta / drug effects
  • Placenta / metabolism
  • Pre-Eclampsia / drug therapy*
  • Pre-Eclampsia / metabolism
  • Pregnancy
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Wistar
  • bcl-2-Associated X Protein / metabolism

Substances

  • Oligopeptides
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Erythropoietin
  • cibinetide
  • NG-Nitroarginine Methyl Ester