Cys-peptide mediates the protective role in preeclampsia-like rat and cell models

Life Sci. 2020 Jun 15:251:117625. doi: 10.1016/j.lfs.2020.117625. Epub 2020 Apr 2.

Abstract

Objective: The present study was designed to investigate whether the novel peptide cysteine-based peptide (Cys-peptide) had protective effects on preeclamptic animal and cell models.

Methods: We investigated effects of Cys-peptide on (1) preeclamptic symptoms (e.g. hypertension, proteinuria, fetal growth restriction (FGR)) in preeclampia-like rat models induced by lipopolysaccharides (LPS), (2) TNFα-induced cytotoxicity of human umbilical vascular endothelial cells (HUVECs) and HTR-8 cells (an immortalised human trophoblast cell line), (3) endothelial dysfunction and injured angiogenesis, (4) migration and invasion of trophoblast cells induced by TNFα.

Results: Cys-peptide ameliorated LPS-induced hypertension, proteinuria and FGR and other PE symptoms in preeclampia-like rat models. In addition, Cys-peptide attenuated TNFα-induced cytotoxicity by decreasing soluble fms-like tyrosine kinase-1 (sFlt-1), endothelin-1 (ET-1) and tissue plasminogen activator (tPA) mRNA expression in both cells. Furthermore, Cys-peptide restored endothelial dysfunction and rescued angiogenesis caused by TNFα in vitro. Importantly, Cys-peptide could reverse insufficient ability to invade and migrate of trophoblast cells.

Conclusions: These results suggest Cys-peptide can play beneficial roles in preeclampsia-like rat and cell models. Therefore, we propose that Cys-peptide is probably a novel therapeutic candidate for PE.

Keywords: Antiangiogenic factors; Cys-peptide; Endothelial injury; Placental dysfunction; Preeclampsia.

MeSH terms

  • Animals
  • Cell Line
  • Cell Movement / drug effects
  • Cysteine / chemistry*
  • Disease Models, Animal
  • Female
  • Fetal Growth Retardation / prevention & control*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hypertension / prevention & control
  • Peptides / administration & dosage*
  • Peptides / chemistry
  • Peptides / pharmacology
  • Pre-Eclampsia / physiopathology
  • Pre-Eclampsia / prevention & control*
  • Pregnancy
  • Proteinuria / prevention & control
  • Rats
  • Rats, Sprague-Dawley
  • Trophoblasts / metabolism
  • Tumor Necrosis Factor-alpha / administration & dosage

Substances

  • Peptides
  • Tumor Necrosis Factor-alpha
  • Cysteine