Lipopolysaccharides (LPS) Induced Angiogenesis During Chicken Embryogenesis is Abolished by Combined ETA/ETB Receptor Blockade

Cell Physiol Biochem. 2018;48(5):2084-2090. doi: 10.1159/000492547. Epub 2018 Aug 10.

Abstract

Background/aims: Angiogenesis plays a key role during embryonic development. The vascular endothelin (ET) system is involved in the regulation of angiogenesis. Lipopolysaccharides (LPS) could induce angiogenesis. The effects of ET blockers on baseline and LPS-stimulated angiogenesis during embryonic development remain unknown so far.

Methods: The blood vessel density (BVD) of chorioallantoic membranes (CAMs), which were treated with saline (control), LPS, and/or BQ123 and the ETB blocker BQ788, were quantified and analyzed using an IPP 6.0 image analysis program. Moreover, the expressions of ET-1, ET-2, ET3, ET receptor A (ETRA), ET receptor B (ETRB) and VEGFR2 mRNA during embryogenesis were analyzed by semi-quantitative RT-PCR.

Results: All components of the ET system are detectable during chicken embryogenesis. LPS increased angiogenesis substantially. This process was completely blocked by the treatment of a combination of the ETA receptor blockers-BQ123 and the ETB receptor blocker BQ788. This effect was accompanied by a decrease in ETRA, ETRB, and VEGFR2 gene expression. However, the baseline angiogenesis was not affected by combined ETA/ETB receptor blockade.

Conclusion: During chicken embryogenesis, the LPS-stimulated angiogenesis, but not baseline angiogenesis, is sensitive to combined ETA/ETB receptor blockade.

Keywords: Angiogenesis; Chicken chorioallantoic membrane (CAM); Endothelin (ET); Lipopolysaccharides (LPS).

MeSH terms

  • Animals
  • Chickens
  • Chorioallantoic Membrane / drug effects
  • Chorioallantoic Membrane / metabolism
  • Embryonic Development / drug effects
  • Endothelin B Receptor Antagonists / pharmacology*
  • Endothelin-1 / genetics
  • Endothelin-1 / metabolism
  • Lipopolysaccharides / pharmacology*
  • Neovascularization, Physiologic / drug effects*
  • Oligopeptides / pharmacology
  • Peptides, Cyclic / pharmacology
  • Piperidines / pharmacology
  • Receptor, Endothelin A / chemistry
  • Receptor, Endothelin A / genetics
  • Receptor, Endothelin A / metabolism*
  • Receptor, Endothelin B / chemistry
  • Receptor, Endothelin B / genetics
  • Receptor, Endothelin B / metabolism*
  • Signal Transduction / drug effects
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Endothelin B Receptor Antagonists
  • Endothelin-1
  • Lipopolysaccharides
  • Oligopeptides
  • Peptides, Cyclic
  • Piperidines
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • BQ 788
  • Vascular Endothelial Growth Factor Receptor-2
  • cyclo(Trp-Asp-Pro-Val-Leu)