Expression of insulin-like growth factor binding protein-3 in HELLP syndrome

BMC Pregnancy Childbirth. 2023 Nov 10;23(1):778. doi: 10.1186/s12884-023-06074-7.

Abstract

Objective: To investigate the expression of insulin-like growth factor binding protein-3(IGFBP-3) in HELLP syndrome and its possible role in the pathogenesis of this disease.

Methods: 1) 87 subjects were enrolled, including 29 patients with HELLP syndrome, 29 patients with pre-eclampsia (PE), and 29 healthy gravidae as control. The levels of IGFBP-3, IGF-1, TGF-β1, and VEGF in maternal and umbilical blood of them were detected using ELISA. Correlation analysis was used to observe the correlation between IGFBP-3 and IGF-1/TGF-β1/VEGF in maternal and umbilical blood, as well as that between maternal serum IGFBP-3 and clinical diagnostic indicators of HELLP syndrome. 2) Human hepatic sinusoid endothelial cells (HLSEC) and human umbilical vein endothelial cells (HUVEC) were cultured with different concentrations of IGFBP-3. After 72 h of culture, cell apoptosis and the normal living cells rate were detected and compared.

Results: 1) In both maternal and umbilical blood of HELLP group, levels of IGFBP-3 and TGF-β1 were higher than control and PE group, IGF-1was lower than control group, VEGF was lower than control and PE group. IGFBP-3 in maternal blood was correlated with IGF-1/TGF-β1/ VEGF, while IGFBP-3 in umbilical blood was linked to IGF-1/TGF-β1. In maternal blood, there was a negative correlation between PLT and IGFBP-3, and a positive correlation between ALT/AST/LDH and IGFBP-3. 2) After cultured with IGFBP-3, the total apoptosis rate of either HLSEC or HUVEC was considerably elevated, while the normal living rate was decreased.

Conclusion: The expression of IGFBP-3 is elevated in HELLP syndrome, which may subsequently promote cell apoptosis by affecting the expression and function of IGF-1, VEGF, and TGFβ1 in the IGF/PI3K/Akt, TGF-β1/Smad3, and VEGF/eNOS/NO pathways. IGFBP-3 aggravates inflammatory reactions of the vascular endothelium and liver under hypoxia, affects the normal function of cells, and plays a role in the pathogenesis of diseases.

Keywords: Endothelial cell; HELLP syndrome; Inflammatory response; Insulin-like growth factor binding protein-3 (IGFBP-3).

MeSH terms

  • Endothelial Cells / metabolism
  • Female
  • HELLP Syndrome*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3* / metabolism
  • Insulin-Like Growth Factor I / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Transforming Growth Factor beta1
  • Vascular Endothelial Growth Factor A

Substances

  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor I
  • Phosphatidylinositol 3-Kinases
  • Transforming Growth Factor beta1
  • Vascular Endothelial Growth Factor A
  • IGFBP3 protein, human